Antigen-dependent and -independent mechanisms of T and B Cell hyperactivation during chronic HIV-1 infection

Journal of Virology

Volumn 85, Issue 23, 2011, Pages 12102-12113

  Haas, Anna ^a   Zimmermann, Kathrin ^a   Oxenius, Annette ^a  

^a ETH ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; GLYCOPROTEIN GP 120; TOLL LIKE RECEPTOR; VIRUS PROTEIN;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANTIGEN FUNCTION; ANTIGEN SPECIFICITY; APOPTOSIS; B LYMPHOCYTE ACTIVATION; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL CYCLE REGULATION; CYTOKINE RELEASE; DENDRITIC CELL; DISEASE COURSE; HOMEOSTASIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HYPERGAMMAGLOBULINEMIA; IMMUNE RESPONSE; IMMUNOPATHOGENESIS; IMMUNOPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SHORT SURVEY; T CELL DEPLETION; T LYMPHOCYTE ACTIVATION; VIRUS REPLICATION;

B-LYMPHOCYTES; HIV INFECTIONS; HIV-1; HUMANS; LYMPHOCYTE ACTIVATION; RECEPTORS, CELL SURFACE; T-LYMPHOCYTES;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 80855161172     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.05607-11     Document Type: Short Survey

References (157)

1. Alimonti, J. B., T. B. Ball, and K. R. Fowke. 2003. Mechanisms of CD4+ T lymphocyte cell death in human immunodeficiency virus infection and AIDS. J. Gen. Virol. 84:1649-1661.
2. Almeida, M., M. Cordero, J. Almeida, and A. Orfao. 2005. Different subsets of peripheral blood dendritic cells show distinct phenotypic and functional abnormalities in HIV-1 infection. AIDS 19:261-271.
3. Anderson, R. W., M. S. Ascher, and H. W. Sheppard. 1998. Direct HIV cytopathicity cannot account for CD4 decline in AIDS in the presence of homeostasis: a worst-case dynamic analysis. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 17:245-252.
4. Appay, V., and D. Sauce. 2008. Immune activation and inflammation in HIV-1 infection: causes and consequences. J. Pathol. 214:231-241.
5. Avice, M. N., et al. 1998. IL-15 promotes IL-12 production by human monocytes via T cell-dependent contact and may contribute to IL-12-mediated IFN-gamma secretion by CD4+ T cells in the absence of TCR ligation. J. Immunol. 161:3408-3415.
6. Bangs, S. C., et al. 2009. Human CD4+ memory T cells are preferential targets for bystander activation and apoptosis. J. Immunol. 182:1962-1971.
7. Bangs, S. C., A. J. McMichael, and X.-N. Xu. 2006. Bystander T cell activation-implications for HIV infection and other diseases. Trends Immunol. 27:518-524.
8. Barron M. A., N. Blyveis, B. E. Palmer, S. MaWhinney, and C. C. Wilson. 2003. Influence of plasma viremia on defects in number and immunophenotype of blood dendritic cell subsets in human immunodeficiency virus 1-infected individuals. J. Infect. Dis. 187:26-37.
9. Bendigs, S., U. Salzer, G. B. Lipford, H. Wagner, and K. Heeg. 1999. CpG-oligodeoxynucleotides co-stimulate primary T cells in the absence of antigen-presenting cells. Eur. J. Immunol. 29:1209-1218.
10. Berberian, L., L. Goodglick, T. J. Kipps, and J. Braun. 1993. Immunoglobulin VH3 gene products: natural ligands for HIV gp120. Science 261:1588-1591.
11. Bernasconi, N. L., N. Onai, and A. Lanzavecchia. 2003. A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells. Blood 101:4500-4504.
12. Bernasconi, N. L., E. Traggiai, and A. Lanzavecchia. 2002. Maintenance of serological memory by polyclonal activation of human memory B cells. Science 298:2199-2202.
13. + T-cell responses: relationship to viral load in untreated HIV infection. J. Virol. 75:11983-11991.
14. Biancotto, A., et al. 2007. Abnormal activation and cytokine spectra in lymph nodes of people chronically infected with HIV-1. Blood 109:4272-4279.
15. Boasso, A., A. W. Hardy, S. A. Anderson, M. J. Dolan, and G. M. Shearer. 2008. HIV-induced type I interferon and tryptophan catabolism drive T cell dysfunction despite phenotypic activation. PLoS One 3:e2961.
16. Bofill, M., et al. 1996. Increased number of primed activated CD8+ CD38+CD45RO+ T cells predict the decline of CD4+ T cells in HIV-1-infected patients. AIDS 10:827-834.
17. Bosinger, S. E., et al. 2009. Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J. Clin. Invest. 119:3556-3572.
18. Bourke, E., D. Bosisio, J. Golay, N. Polentarutti, and A. Mantovani. 2003. The toll-like receptor repertoire of human B lymphocytes: inducible and selective expression of TLR9 and TLR10 in normal and transformed cells. Blood 102:956-963.
19. Brenchley, J. M., and D. C. Douek. 2008. HIV infection and the gastrointestinal immune system. Mucosal Immunol. 1:23-30.
20. Brenchley, J. M., et al. 2006. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat. Med. 12:1365-1371.
21. Brenchley, J. M., et al. 2004. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J. Exp. Med. 200:749-759.
22. Bucy, R. P., et al. 1999. Initial increase in blood CD4+ lymphocytes after HIV antiretroviral therapy reflects redistribution from lymphoid tissues. J. Clin. Invest. 103:1391-1398.
23. Caron, G., et al. 2005. Direct stimulation of human T cells via TLR5 and TLR7/8: flagellin and R-848 up-regulate proliferation and IFN-gamma production by memory CD4+ T cells. J. Immunol. 175:1551-1557.
24. Catalfamo, M., et al. 2008. HIV infection-associated immune activation occurs by two distinct pathways that differentially affect CD4 and CD8 T cells. Proc. Natl. Acad. Sci. U. S. A. 105:19851-19856.
25. Catalfamo, M., et al. 2011. CD4 and CD8 T cell immune activation during chronic HIV infection: roles of homeostasis, HIV, type I IFN, and IL-7. J. Immunol. 186:2106-2116.
26. Chirmule, N., N. Oyaizu, C. Saxinger, and S. Pahwa. 1994. Nef protein of HIV-1 has B-cell stimulatory activity. AIDS 8:733-734.
27. Cottalorda, A., et al. 2009. TLR2 engagement on memory CD8+ T cells improves their cytokine-mediated proliferation and IFN-γ secretion in the absence of Ag. Eur. J. Immunol. 39:2673-2681.
28. Cottalorda, A., et al. 2006. TLR2 engagement on CD8 T cells lowers the threshold for optimal antigen-induced T cell activation. Eur. J. Immunol. 36:1684-1693.
29. Cotton, M. F., et al. 1996. Apoptosis in HIV-1 infection. Behring Inst. Mitt. 97:220-231.
30. Deeks, S. G., et al. 2004. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood 104:942-947.
31. De Milito, A., et al. 2004. Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection. Blood 103:2180-2186.
32. Di Domizio, J., et al. 2009. TLR7 stimulation in human plasmacytoid dendritic cells leads to the induction of early IFN-inducible genes in the absence of type I IFN. Blood 114:1794-1802.
33. Dillon, S. M., et al. 2008. Plasmacytoid and myeloid dendritic cells with a partial activation phenotype accumulate in lymphoid tissue during asymptomatic chronic human immunodeficiency virus type 1 infection. J. Acquir. Immune Defic. Syndr. 48:1-12.
34. Doisne J.-M., et al. 2004. CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection. J. Immunol. 173:2410-2418.
35. Dornadula, G., H. Zhang, S. Shetty, and R. J. Pomerantz. 1999. HIV-1 virions produced from replicating peripheral blood lymphocytes are more infectious than those from nonproliferating macrophages due to higher levels of intravirion reverse transcripts: implications for pathogenesis and transmission. Virology 253:10-16.
36. Douek, D. C., L. J. Picker, and R. A. Koup. 2003. T cell dynamics in HIV-1 infection. Annu. Rev. Immunol. 21:265-304.
37. Douek, D. C., et al. 2002. HIV preferentially infects HIV-specific CD4+ T cells. Nature 417:95-98.
38. Eller, M. A., et al. 2011. Innate and adaptive immune responses both contribute to pathological CD4 T cell activation in HIV-1 infected Ugandans. PLoS One 6:e18779.
39. Embretson, J., et al. 1993. Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS. Nature 362:359-362.
40. Estes, J. D., et al. 2010. Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog. 6:e1001052.
41. Favre, D., et al. 2010. Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci. Transl. Med. 2:32ra36.
42. Fecteau, J. F., and S. Néron. 2003. CD40 stimulation of human peripheral B lymphocytes: distinct response from naive and memory cells. J. Immunol. 171:4621-4629.
43. Finkel, T. H., et al. 1995. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes. Nat. Med. 1:129-134.
44. Fitzgerald-Bocarsly, P., and E. S. Jacobs. 2010. Plasmacytoid dendritic cells in HIV infection: striking a delicate balance. J. Leukoc. Biol. 87:609-620.
45. Fleury, S., et al. 2000. Long-term kinetics of T cell production in HIVinfected subjects treated with highly active antiretroviral therapy. Proc. Natl. Acad. Sci. U. S. A. 97:5393-5398.
46. Flø, R. W., A. Nilsen, P. Voltersvik, and G. Haukenes. 1993. Serum antibodies to viral pathogens and Toxoplasma gondii in HIV-infected individuals. APMIS 101:946-952.
47. Fournier, A. M., et al. 2002. Spontaneous secretion of immunoglobulins and anti-HIV-1 antibodies by in vivo activated B lymphocytes from HIV-1-infected subjects: monocyte and natural killer cell requirement for in vitro terminal differentiation into plasma cells. Clin. Immunol. 103:98-109.
48. Fry, T. J., and C. L. Mackall. 2001. Interleukin-7: master regulator of peripheral T-cell homeostasis? Trends Immunol. 22:564-571.
49. Funderburg, N., et al. 2008. Toll-like receptor ligands induce human T cell activation and death, a model for HIV pathogenesis. PLoS One 3:e1915.
50. + suppressor T cells in vivo. Nat. Immunol. 3:33-41.
51. Giorgi, J. V., et al. 1999. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J. Infect. Dis. 179:859-870.
52. Goldrath, A. W., and M. J. Bevan. 1999. Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts. Immunity 11:183-190.
53. Gordon, S. N., et al. 2010. Disruption of intestinal CD4+ T cell homeostasis is a key marker of systemic CD4+ T cell activation in HIV-infected individuals. J. Immunol. 185:5169-5179.
54. Gougeon M. L., et al. 1996. Programmed cell death in peripheral lymphocytes from HIV-infected persons: increased susceptibility to apoptosis of CD4 and CD8 T cells correlates with lymphocyte activation and with disease progression. J. Immunol. 156:3509-3520. inelevel1
55. Grossman, Z., M. B. Feinberg, and W. E. Paul. 1998. Multiple modes of cellular activation and virus transmission in HIV infection: a role for chronically and latently infected cells in sustaining viral replication. Proc. Natl. Acad. Sci. U. S. A. 95:6314-6319.
56. Grossman, Z., M. Meier-Schellersheim, W. E. Paul, and L. J. Picker. 2006. Pathogenesis of HIV infection: what the virus spares is as important as what it destroys. Nat. Med. 12:289-295.
57. Guadalupe, M., et al. 2003. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J. Virol. 77:11708-11717.
58. Gudmundsdottir, H., and L. A. Turka. 2001. A closer look at homeostatic proliferation of CD4+ T cells: costimulatory requirements and role in memory formation. J. Immunol. 167:3699-3707.
59. Haas, A., et al. 2010. HIV-1 replication activates CD4+ T cells with specificities for persistent herpes viruses. EMBO Mol. Med. 2:231-244.
60. Haas, A., et al. 21 April 2011. Systemic antibody responses to gut commensal bacteria during chronic HIV-1 infection. Gut [Epub ahead of print.] doi:10.1136/gut.2010.224774.
61. Hakim, F. T., et al. 1997. Constraints on CD4 recovery postchemotherapy in adults: thymic insufficiency and apoptotic decline of expanded peripheral CD4 cells. Blood 90:3789-3798.
62. Harman, A. N., et al. 2006. HIV induces maturation of monocyte-derived dendritic cells and Langerhans cells. J. Immunol. 177:7103-7113.
63. Harper, M. E., L. M. Marselle, R. C. Gallo, and F. Wong-Staal. 1986. Detection of lymphocytes expressing human T-lymphotropic virus type III in lymph nodes and peripheral blood from infected individuals by in situ hybridization. Proc. Natl. Acad. Sci. U. S. A. 83:772-776.
64. Hart, M., et al. 2007. Loss of discrete memory B cell subsets is associated with impaired immunization responses in HIV-1 infection and may be a risk factor for invasive pneumococcal disease. J. Immunol. 178:8212-8220.
65. Haynes, B. F., et al. 2005. Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science 308:1906-1908.
66. Hazenberg, M. D., D. Hamann, H. Schuitemaker, and F. Miedema. 2000. T cell depletion in HIV-1 infection: how CD4+ T cells go out of stock. Nat. Immunol. 1:285-289.
67. Hazenberg, M. D., et al. 2003. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS 17:1881-1888.
68. Hazenberg, M. D., et al. 2000. T-cell division in human immunodeficiency virus (HIV)-1 infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active antiretroviral therapy (HAART). Blood 95:249-255.
69. He, B., et al. 2006. HIV-1 envelope triggers polyclonal Ig class switch recombination through a CD40-independent mechanism involving BAFF and C-type lectin receptors. J. Immunol. 176:3931-3941.
70. Hellerstein, M. K., and J. M. McCune. 1997. T cell turnover in HIV-1 disease. Immunity 7:583-589.
71. Ho, D. D., et al. 1995. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123-126.
72. Hopkins, P. A., and S. Sriskandan. 2005. Mammalian Toll-like receptors: to immunity and beyond. Clin. Exp. Immunol. 140:395-407.
73. Huang, L., C. J. Li, and A. B. Pardee. 1997. Human immunodeficiency virus type 1 TAT protein activates B lymphocytes. Biochem. Biophys. Res. Commun. 237:461-464.
74. Hunt, P. W., et al. 2011. A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers. PLoS One 6:e15924.
75. Hunziker, L., et al. 2003. Hypergammaglobulinemia and autoantibody induction mechanisms in viral infections. Nat. Immunol. 4:343-349.
76. Jacquelin, B., et al. 2009. Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. J. Clin. Invest. 119:3544-3555.
77. Jameson, S. C. 2002. Maintaining the norm: T-cell homeostasis. Nat. Rev. Immunol. 2:547-556.
78. Jamieson, B. D., et al. 1999. Generation of functional thymocytes in the human adult. Immunity 10:569-575.
79. Kabelitz, D. 2007. Expression and function of Toll-like receptors in T lymphocytes. Curr. Opin. Immunol. 19:39-45.
80. Kaiser, P., et al. 2007. Productive human immunodeficiency virus type 1 infection in peripheral blood predominantly takes place in CD4/CD8 double-negative T lymphocytes. J. Virol. 81:9693-9706.
81. Kanai, T., E. K. Thomas, Y. Yasutomi, and N. L. Letvin. 1996. IL-15 stimulates the expansion of AIDS virus-specific CTL. J. Immunol. 157: 3681-3687.
82. Karray, S., and M. Zouali. 1997. Identification of the B cell superantigenbinding site of HIV-1 gp120. Proc. Natl. Acad. Sci. U. S. A. 94:1356-1360.
83. Keating, J., et al. 1995. Intestinal absorptive capacity, intestinal permeability and jejunal histology in HIV and their relation to diarrhoea. Gut 37: 623-629.
84. Kelleher, A. D., A. Carr, J. Zaunders, and D. A. Cooper. 1996. Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir. J. Infect. Dis. 173:321-329.
85. Kindler, V., and R. H. Zubler. 1997. Memory, but not naive, peripheral blood B lymphocytes differentiate into Ig-secreting cells after CD40 ligation and costimulation with IL-4 and the differentiation factors IL-2, IL-10, and IL-3. J. Immunol. 159:2085-2090.
86. Komai-Koma, M., L. Jones, G. S. Ogg, D. Xu, and F. Y. Liew. 2004. TLR2 is expressed on activated T cells as a costimulatory receptor. Proc. Natl. Acad. Sci. U. S. A. 101:3029-3034.
87. Kotler, D. P., H. P. Gaetz, M. Lange, E. B. Klein, and P. R. Holt. 1984. Enteropathy associated with the acquired immunodeficiency syndrome. Ann. Intern. Med. 101:421-428.
88. Kovacs, J. A., et al. 2001. Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV. J. Exp. Med. 194:1731-1741.
89. Lane, H. C., et al. 1983. Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N. Engl. J. Med. 309:453-458.
90. Lefevre, E. A., R. Krzysiek, E. P. Loret, P. Galanaud, and Y. Richard. 1999. Cutting edge: HIV-1 Tat protein differentially modulates the B cell response of naive, memory, and germinal center B cells. J. Immunol. 163: 1119-1122.
91. Levesque, M. C., et al. 2009. Polyclonal B cell differentiation and loss of gastrointestinal tract germinal centers in the earliest stages of HIV-1 infection. PLoS Med. 6:e1000107.
92. Li, Q.-J., et al. 2004. CD4 enhances T cell sensitivity to antigen by coordinating Lck accumulation at the immunological synapse. Nat. Immunol. 5:791-799.
93. Lisco, A., C. Vanpouille, and L. Margolis. 2009. War and peace between microbes: HIV-1 interactions with coinfecting viruses. Cell Host Microbe 6:403-408.
94. Liu, K., M. Catalfamo, Y. Li, P. A. Henkart, and N.-p. Weng. 2002. IL-15 mimics T cell receptor crosslinking in the induction of cellular proliferation, gene expression, and cytotoxicity in CD8+ memory T cells. Proc. Natl. Acad. Sci. U. S. A. 99:6192-6197.
95. Loré, K., et al. 2003. Toll-like receptor ligands modulate dendritic cells to augment cytomegalovirus- and HIV-1-specific T cell responses. J. Immunol. 171:4320-4328.
96. Malaspina, A., et al. 2008. CpG oligonucleotides enhance proliferative and effector responses of B cells in HIV-infected individuals. J. Immunol. 181: 1199-1296.
97. Malaspina, A., et al. 2003. Deleterious effect of HIV-1 plasma viremia on B cell costimulatory function. J. Immunol. 170:5965-5972.
98. Malaspina, A., et al. 2005. Compromised B cell responses to influenza vaccination in HIV-infected individuals. J. Infect. Dis. 191:1442-1450.
99. Malisan, F., et al. 1996. Interleukin-10 induces immunoglobulin G isotype switch recombination in human CD40-activated naive B lymphocytes. J. Exp. Med. 183:937-947.
100. McGowan, I., et al. 2004. Increased HIV-1 mucosal replication is associated with generalized mucosal cytokine activation. J. Acquir. Immune Defic. Syndr. 37:1228-1236.
101. Mehandru, S., et al. 2004. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J. Exp. Med. 200:761-770.
102. Mohri, H., S. Bonhoeffer, S. Monard, A. Perelson, and D. Ho. 1998. Rapid turnover of T lymphocytes in SIV-infected rhesus macaques. Science 279: 1223-1227.
103. Mohri, H., et al. 2001. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J. Exp. Med. 194:1277-1287.
104. Moir, S., et al. 2000. B cells of HIV-1-infected patients bind virions through CD21-complement interactions and transmit infectious virus to activated T cells. J. Exp. Med. 192:637-646.
105. Moir, S., and A. S. Fauci. 2009. B cells in HIV infection and disease. Nat. Rev. Immunol. 9:235-245.
106. Müller, F., P. Aukrust, I. Nordoy, and S. S. Froland. 1998. Possible role of interleukin-10 (IL-10) and CD40 ligand expression in the pathogenesis of hypergammaglobulinemia in human immunodeficiency virus infection: modulation of IL-10 and Ig production after intravenous Ig infusion. Blood 92:3721-3729.
107. Murali-Krishna, K., et al. 1998. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 8:177-187.
108. Napolitano, L. A., et al. 2001. Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis. Nat. Med. 7:73-79.
109. Nazli, A., et al. 2010. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathog. 6:e1000852.
110. Ng, V. L. 1996. B-lymphocytes and autoantibody profiles in HIV disease. Clin. Rev. Allergy Immunol. 14:367-384.
111. Nilssen, D. E., O. Øktedalen, and P. Brandtzaeg. 2004. Intestinal B cell hyperactivity in AIDS is controlled by highly active antiretroviral therapy. Gut 53:487-493.
112. Oehen, S., and K. Brduscha-Riem. 1998. Differentiation of naive CTL to effector and memory CTL: correlation of effector function with phenotype and cell division. J. Immunol. 161:5338-5346.
113. Oravecz, T., and M. A. Norcross. 1993. Costimulatory properties of the human CD4 molecule: enhancement of CD3-induced T cell activation by human immunodeficiency virus type 1 through viral envelope glycoprotein gp120. AIDS Res. Hum. Retroviruses 9:945-955.
114. Pantaleo G., et al. 1994. Role of lymphoid organs in the pathogenesis of human immunodeficiency virus (HIV) infection. Immunol. Rev. 140:105-130.
115. Papagno, L., et al. 2004. Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol. 2:E20.
116. Patki, A., et al. 1996. Activation of antigen-induced lymphocyte proliferation by interleukin-15 without the mitogenic effect of interleukin-2 that may induce human immunodeficiency virus-1 expression. J. Clin. Invest. 98:616-621.
117. Pinching, A. J. 1991. Antibody responses in HIV infection. Clin. Exp. Immunol. 84:181-184.
118. Qiao, X., et al. 2006. Human immunodeficiency virus 1 Nef suppresses CD40-dependent immunoglobulin class switching in bystander B cells. Nat. Immunol. 7:302-310.
119. Quaranta, M. G., B. Camponeschi, E. Straface, W. Malorni, and M. Viora. 1999. Induction of interleukin-15 production by HIV-1 Nef protein: a role in the proliferation of uninfected cells. Exp. Cell Res. 250:112-121.
120. Quesnel, A., et al. 1993. Prognostic value of serum immunoglobulin A antibodies to pol gene products during HIV-1 infection. Clin. Exp. Immunol. 91:237-240.
121. Racz, P., et al. 1990. Lymphatic tissue changes in AIDS and other retrovirus infections: tools and insights. Lymphology 23:85-91.
122. Rappocciolo, G., et al. 2006. DC-SIGN on B lymphocytes is required for transmission of HIV-1 to T lymphocytes. PLoS Pathog. 2:e70.
123. Rawson, P. M., et al. 2007. Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection. Nat. Med. 13:1431-1439.
124. Rieckmann, P., G. Poli, C. H. Fox, J. H. Kehrl, and A. S. Fauci. 1991. Recombinant gp120 specifically enhances tumor necrosis factor-alpha production and Ig secretion in B lymphocytes from HIV-infected individuals but not from seronegative donors. J. Immunol. 147:2922-2927.
125. Rodriguez, B., M. M. Lederman, W. Jiang, D. A. Bazdar, K. Gàrate, C. V. Harding, and S. F. Sieg. 2006. Interferon-α differentially rescues CD4 and CD8 T cells from apoptosis in HIV infection. AIDS 20:1379-1389.
126. Rosenzweig, M., et al. 1998. Increased rates of CD4+ and CD8+ T lymphocyte turnover in simian immunodeficiency virus-infected macaques. Proc. Natl. Acad. Sci. U. S. A. 95:6388-6393.
127. Ruprecht, C. R., and A. Lanzavecchia. 2006. Toll-like receptor stimulation as a third signal required for activation of human naive B cells. Eur. J. Immunol. 36:810-816.
128. Sharpstone, D., et al. 1999. Small intestinal transit, absorption, and permeability in patients with AIDS with and without diarrhoea. Gut 45:70-76.
129. Shirai, A., M. Cosentino, S. F. Leitman-Klinman, and D. M. Klinman. 1992. Human immunodeficiency virus infection induces both polyclonal and virus-specific B cell activation. J. Clin. Invest. 89:561-566.
130. Sieg, S. F., et al. 2005. Peripheral S-phase T cells in HIV disease have a central memory phenotype and rarely have evidence of recent T cell receptor engagement. J. Infect. Dis. 192:62-70.
131. Simmons, A., V. Aluvihare, and A. McMichael. 2001. Nef triggers a transcriptional program in T cells imitating single-signal T cell activation and inducing HIV virulence mediators. Immunity 14:763-777.
132. Sopper S., et al. 2003. Impact of simian immunodeficiency virus (SIV) infection on lymphocyte numbers and T-cell turnover in different organs of rhesus monkeys. Blood 101:1213-1219.
133. Sousa, A. E., J. Carneiro, M. Meier-Schellersheim, Z. Grossman, and R. M. M. Victorino. 2002. CD4 T cell depletion is linked directly to immune activation in the pathogenesis of HIV-1 and HIV-2 but only indirectly to the viral load. J. Immunol. 169:3400-3406.
134. Sprent, J., and D. F. Tough. 1994. Lymphocyte life-span and memory. Science 265:1395-1400.
135. Sprent, J., X. Zhang, S. Sun, and D. Tough. 1999. T-cell turnover in vivo and the role of cytokines. Immunol. Lett. 65:21-25.
136. Srinivasula, S., et al. 2011. Differential effects of HIV viral load and CD4 count on proliferation of naive and memory CD4 and CD8 T lymphocytes. Blood 118:262-270.
137. Stacey, A. R., et al. 2009. Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J. Virol. 83:3719-3733.
138. Stein, T. P., et al. 1997. Weight loss, the gut and the inflammatory response in AIDS patients. Cytokine 9:143-147.
139. Stohl, W., et al. 2002. B lymphocyte stimulator protein-associated increase in circulating autoantibody levels may require CD4+ T cells: lessons from HIV-infected patients. Clin. Immunol. 104:115-122.
140. Sun, S., X. Zhang, D. Tough, and J. Sprent. 2000. Multiple effects of immunostimulatory DNA on T cells and the role of type I interferons. Springer Semin. Immunopathol. 22:77-84.
141. Surh, C. D., and J. Sprent. 2000. Homeostatic T cell proliferation: how far can T cells be activated to self-ligands? J. Exp. Med. 192:F9-F14.
142. Swingler, S., et al. 2008. Evidence for a pathogenic determinant in HIV-1 Nef involved in B cell dysfunction in HIV/AIDS. Cell Host Microbe 4:63-76.
143. Swingler, S., B. Brichacek, J.-M. Jacque, and C. Ulich. 2003. HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote restingcell infection. Nature 424:213-219.
144. Tanchot, C., A. Le Campion, S. Léaument, N. Dautigny, and B. Lucas. 2001. Naive CD4+ lymphocytes convert to anergic or memory-like cells in T cell-deprived recipients. Eur. J. Immunol. 31:2256-2265.
145. Tangye, S. G., D. T. Avery, E. K. Deenick, and P. D. Hodgkin. 2003. Intrinsic differences in the proliferation of naive and memory human B cells as a mechanism for enhanced secondary immune responses. J. Immunol. 170: 686-694.
146. Tough, D. F., and J. Sprent. 1998. Bystander stimulation of T cells in vivo by cytokines. Vet. Immunol. Immunopathol. 63:123-129.
147. Tough, D. F., S. Sun, and J. Sprent. 1997. T cell stimulation in vivo by lipopolysaccharide (LPS). J. Exp. Med. 185:2089-2094.
148. Tough, D. F., P. Borrow, and J. Sprent. 1996. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272:1947-1950.
149. Unutmaz, D., P. Pileri, and S. Abrignani. 1994. Antigen-independent activation of naive and memory resting T cells by a cytokine combination. J. Exp. Med. 180:1159-1164.
150. Veazey, R., et al. 1998. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science 280:427-431.
151. Wagner, M., et al. 2004. IL-12p70-dependent Th1 induction by human B cells requires combined activation with CD40 ligand and CpG DNA. J. Immunol. 172:954-963.
152. Waldrop, S. L., C. J. Pitcher, D. M. Peterson, V. C. Maino, and L. J. Picker. 1997. Determination of antigen-specific memory/effector CD4+ T cell frequencies by flow cytometry: evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency. J. Clin. Invest. 99: 1739-1750.
153. Weber, R., et al. 1999. Enteric infections and diarrhea in human immunodeficiency virus-infected persons: prospective community-based cohort study. Arch. Intern. Med. 159:1473-1480.
154. Wilson, C. M., J. H. Ellenberg, S. D. Douglas, A.-B. Moscicki, and C. A. Holland. 2004. CD8+CD38+ T cells but not HIV type 1 RNA viral load predict CD4+ T cell loss in a predominantly minority female HIV+ adolescent population. AIDS Res. Hum. Retroviruses 20:263-269.
155. Xu, W., et al. 2009. HIV-1 evades virus-specific IgG2 and IgA responses by targeting systemic and intestinal B cells via long-range intercellular conduits. Nat. Immunol. 10:1008-1017.
156. Zeng, M., A. Smith, and S. Wietgrefe. 2011. Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections. J. Clin. Invest. 121:998-1008.
157. Zhang, Z., et al. 2011. B and T lymphocyte attenuator down-regulation by HIV-1 depends on type I interferon and contributes to T-cell hyperactivation. J. Infect. Dis. 203:1668-1678.