FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection

Journal of Leukocyte Biology

Volumn 83, Issue 2, 2008, Pages 254-262

  Ndhlovu, Lishomwa C ^a   Loo, Christopher P ^a   Spotts, Gerald ^b   Nixon, Douglas F ^a   Hecht, Frederick M ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

AIDS; Immunosuppression; Regulation; Viral

Indexed keywords

CD38 ANTIGEN; INTERLEUKIN 7 RECEPTOR; TRANSCRIPTION FACTOR FOXP3;

ARTICLE; CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL POPULATION; CELL PROLIFERATION; CONTROLLED STUDY; DISEASE COURSE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; IMMUNE STATUS; IMMUNOPHENOTYPING; IMMUNOSUPPRESSIVE TREATMENT; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; VIRUS LOAD; VIRUS REPLICATION;

ANTIGENS, CD38; CD4 LYMPHOCYTE COUNT; CD8-POSITIVE T-LYMPHOCYTES; CELL DIVISION; DISEASE PROGRESSION; FORKHEAD TRANSCRIPTION FACTORS; HIV INFECTIONS; HIV-1; HUMANS; IMMUNOPHENOTYPING; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; INTERLEUKIN-7 RECEPTOR ALPHA SUBUNIT; LYMPHOCYTE ACTIVATION; MEMBRANE GLYCOPROTEINS; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 38949128315     PISSN: 07415400     EISSN: None     Source Type: Journal    
DOI: 10.1189/jlb.0507281     Document Type: Article

References (67)

1. Hazenberg, M. D., Stuart, J. W., Otto, S. A., Borleffs, J. C., Boucher, C. A., de Boer, R. J., Miedema, F., Hamann, D. (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.
2. Deeks, S. G., Kitchen, C. M., Liu, L., Guo, H., Gascon, R., Narvaez, A. B., Hunt, P., Martin, J. N., Kahn, J. O., Levy, J., McGrath, M. S., Hecht, F. M. (2004) Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood 104, 942-947.
3. Eggena, M. P., Barugahare, B., Jones, N., Okello, M., Mutalya, S., Kityo, C., Mugyenyi, P., Cao, H. (2005) Depletion of regulatory T cells in HIV infection is associated with immune activation. J. Immunol. 174, 4407-4414.
4. Papagno, L., Spina, C. A., Marchant, A., Salio, M., Rufer, N., Little, S., Dong, T., Chesney, G., Waters, A., Easterbrook, P., Dunbar, P. R., Shepherd, D., Cerundolo, V., Emery, V., Griffiths, P., Conlon, C., McMichael, A. J., Richman, D. D., Rowland-Jones, S. L., Appay, V. (2004) Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol. 2, E20.
5. Hazenberg, M. D., Otto, S. A., van Benthem, B. H., Roos, M. T., Coutinho, R. A., Lange, J. M., Hamann, D., Prins, M., Miedema, F. (2003) Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS 17, 1881-1888.
6. Lane, H. C., Masur, H., Edgar, L. C., Whalen, G., Rook, A. H., Fauci, A. S. (1983) Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N. Engl. J. Med. 309, 453-458.
7. Sousa, A. E., Carneiro, J., Meier-Schellersheim, M., Grossman, Z., Victorino, R. M. (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.
8. Brenchley, J. M., Price, D. A., Schacker, T. W., Asher, T. E., Silvestri, G., Rao, S., Kazzaz, Z., Bornstein, E., Lambotte, O., Altmann, D., Blazar, B. R., Rodriguez, B., Teixeira-Johnson, L., Landay, A., Martin, J. N., Hecht, F. M., Picker, L. J., Lederman, M. M., Deeks, S. G., Douek, D. C. (2006) Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat. Med. 12, 1365-1371.
9. Mohri, H., Perelson, A. S., Tung, K., Ribeiro, R. M., Ramratnam, B., Markowitz, M., Kost, R., Hurley, A., Weinberger, L., Cesar, D., Hellerstein, M. K., Ho, D. D. (2001) Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J. Exp. Med. 194, 1277-1287.
10. Giorgi, J. V., Hultin, L. E., McKeating, J. A., Johnson, T. D., Owens, B., Jacobson, L. P., Shih, R., Lewis, J., Wiley, D. J., Phair, J. P., Wolinsky, S. M., Detels, R. (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.
11. Giorgi, J. V., Liu, Z., Hultin, L. E., Cumberland, W. G., Hennessey, K., Detels, R. (1993) Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6 years of follow-up. The Los Angeles Center, Multicenter AIDS Cohort Study. J. Acquir. Immune Defic. Syndr. 6, 904-912.
12. Rodriguez, B., Sethi, A. K., Cheruvu, V. K., Mackay, W., Bosch, R. J., Kitahata, M., Boswell, S. L., Mathews, W. C., Bangsberg, D. R., Martin, J., Whalen, C. C., Sieg, S., Yadavalli, S., Deeks, S. G., Lederman, M. M. (2006) Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA 296, 1498-1506.
13. Cauley, L. S., Miller, E. E., Yen, M., Swain, S. L. (2000) Superantigen-induced CD4 T cell tolerance mediated by myeloid cells and IFN-γ. J. Immunol. 165, 6056-6066.
14. Paccani, S. R., Tonello, F., Ghittoni, R., Natale, M., Muraro, L., D'Elios, M. M., Tang, W. J., Montecucco, C., Baldari, C. T. (2005) Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling. J. Exp. Med. 201, 325-331.
15. Moura, A. C., Mariano, M. (1997) Lipids from Mycobacterium leprae cell wall suppress T-cell activation in vivo and in vitro. Immunology 92, 429-436.
16. Lohr, J., Knoechel, B., Jiang, S., Sharpe, A. H., Abbas, A. K. (2003) The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens. Nat. Immunol. 4, 664-669.
17. Rosini, L., Matlack, R., Taylor, J., Howell, K. F., Yeh, K., Pennello, A., Riggs, J. E. (2004) Nonlymphoid peritoneal cells suppress the T cell response to Mls. Immunobiology 209, 575-584.
18. Boyer, O., Saadoun, D., Abriol, J., Dodille, M., Piette, J. C., Cacoub, P., Klatzmann, D. (2004) CD4+CD25+ regulatory T-cell deficiency in patients with hepatitis C-mixed cryoglobulinemia vasculitis. Blood 103, 3428-3430.
19. Long, T. T., Nakazawa, S., Onizuka, S., Huaman, M. C., Kanbara, H. (2003) Influence of CD4+CD25+ T cells on Plasmodium berghei NK65 infection in BALB/c mice. Int. J. Parasitol. 33, 175-183.
20. Stoop, J. N., van der Molen, R. G., Baan, C. C., van der Laan, L. J., Kuipers, E. J., Kusters, J. G., Janssen, H. L. (2005) Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection. Hepatology 41, 771-778.
21. Franzese, O., Kennedy, P. T., Gehring, A. J., Gotto, J., Williams, R., Maini, M. K., Bertoletti, A. (2005) Modulation of the CD8+-T-cell response by CD4+ CD25+ regulatory T cells in patients with hepatitis B virus infection. J. Virol. 79, 3322-3328.
22. Sugimoto, K., Ikeda, F., Stadanlick, J., Nunes, F. A., Alter, H. J., Chang, K. M. (2003) Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection. Hepatology 38, 1437-1448.
23. Hisaeda, H., Maekawa, Y., Iwakawa, D., Okada, H., Himeno, K., Kishihara, K., Tsukumo, S., Yasutomo, K. (2004) Escape of malaria parasites from host immunity requires CD4+ CD25+ regulatory T cells. Nat. Med. 10, 29-30.
24. Aandahl, E. M., Michaelsson, J., Moretto, W. J., Hecht, F. M., Nixon, D. F. (2004) Human CD4+ CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens. J. Virol. 78, 2454-2459.
25. Lim, A.Y., Price, P., Beilharz, M.W., French, M.A. (2006) Cell surface markers of regulatory T cells are not associated with increased forkhead box p3 expression in blood CD4(+) T cells from HIV-infected patients responding to antiretroviral therapy. Immunol. Cell Biol. 84, 530-536.
26. Epple, H. J., Loddenkemper, C., Kunkel, D., Troger, H., Maul, J., Moos, V., Berg, E., Ullrich, R., Schulzke, J. D., Stein, H., Duchmann, R., Zeitz, M., Schneider, T. (2006) Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART. Blood 108, 3072-3078.
27. Apoil, P. A., Puissant, B., Roubinet, F., Abbal, M., Massip, P., Blancher, A. (2005) FOXP3 mRNA levels are decreased in peripheral blood CD4+ lymphocytes from HIV-positive patients. J. Acquir. Immune Defic. Syndr. 39, 381-385.
28. Zaunders, J. J., Ip, S., Munier, M. L., Kaufmann, D. E., Suzuki, K., Brereton, C., Sasson, S. C., Seddiki, N., Koelsch, K., Landay, A., Grey, P., Finlayson, R., Kaldor, J., Rosenberg, E. S., Walker, B. D., Fazekas de St Groth, B., Cooper, D. A., Kelleher, A. D. (2006) Infection of CD127+ (interleukin-7 receptor+) CD4+ cells and overexpression of CTLA-4 are linked to loss of antigen-specific CD4 T cells during primary human immunodeficiency virus type 1 infection. J. Virol. 80, 10162-10172.
29. Weiss, L., Donkova-Petrini, V., Caccavelli, L., Balbo, M., Carbonneil, C., Levy, Y. (2004) Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients. Blood 104, 3249-3256.
30. Oswald-Richter, K., Grill, S. M., Shariat, N., Leelawong, M., Sundrud, M. S., Haas, D. W., Unutmaz, D. (2004) HIV infection of naturally occurring and genetically reprogrammed human regulatory T-cells. PLoS Biol. 2, E198.
31. Tsunemi, S., Iwasaki, T., Imado, T., Higasa, S., Kakishita, E., Shirasaka, T., Sano, H. (2005) Relationship of CD4+CD25+ regulatory T cells to immune status in HIV-infected patients. AIDS 19, 879-886.
32. Kinter, A. L., Hennessey, M., Bell, A., Kern, S., Lin, Y., Daucher, M., Planta, M., McGlaughlin, M., Jackson, R., Ziegler, S. F., Fauci, A. S. (2004) CD25(+)CD4(+) regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4(+) and CD8(+) HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status. J. Exp. Med. 200, 331-343.
33. Andersson, J., Boasso, A., Nilsson, J., Zhang, R., Shire, N. J., Lindback, S., Shearer, G. M., Chougnet, C. A. (2005) The prevalence of regulatory T cells in lymphoid tissue is correlated with viral load in HIV-infected patients. J. Immunol. 174, 3143-3147.
34. Montes, M., Lewis, D. E., Sanchez, C., de Castilla, D. L., Graviss, E. A., Seas, C., Gotuzzo, E., White Jr., A. C. (2006) Foxp3+ regulatory T cells in antiretroviral-naive HIV patients. AIDS 20, 1669-1671.
35. Michaelsson, J., Mold, J. E., McCune, J. M., Nixon, D. F. (2006) Regulation of T cell responses in the developing human fetus. J. Immunol. 176, 5741-5748.
36. Seddiki, N., Santner-Nanan, B., Martinson, J., Zaunders, J., Sasson, S., Landay, A., Solomon, M., Selby, W., Alexander, S. I., Nanan, R., Kelleher, A., Fazekas de St Groth, B. (2006) Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 203, 1693-1700.
37. Liu, W., Putnam, A. L., Xu-Yu, Z., Szot, G. L., Lee, M. R., Zhu, S., Gottlieb, P. A., Kapranov, P., Gingeras, T. R., Fazekas de St Groth, B., Clayberger, C., Soper, D. M., Ziegler, S. F., Bluestone, J. A. (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J. Exp. Med. 203, 1701-1711.
38. Raimondi, G., Shufesky, W. J., Tokita, D., Morelli, A. E., Thomson, A. W. (2006) Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ resting regulatory T cells from activated T cells. J. Immunol. 176, 2808-2816.
39. Janssen, R. S., Satten, G. A., Stramer, S. L., Rawal, B. D., O'Brien, T. R., Weiblen, B. J., Hecht, F. M., Jack, N., Cleghorn, F. R., Kahn, J. O., Chesney, M. A., Busch, M. P. (1998) New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes. JAMA 280, 42-48.
40. Kothe, D., Byers, R. H., Caudill, S. P., Satten, G. A., Janssen, R. S., Hannon, W. H., Mei, J. V. (2003) Performance characteristics of a new less sensitive HIV-1 enzyme immunoassay for use in estimating HIV seroincidence. J. Acquir. Immune Defic. Syndr. 33, 625-634.
41. Shimizu, J., Yamazaki, S., Takahashi, T., Ishida, Y., Sakaguchi, S. (2002) Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol. 3, 135-142.
42. Hori, S., Nomura, T., Sakaguchi, S. (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057-1061.
43. Ndhlovu, L. C., Takeda, I., Sugamura, K., Ishii, N. (2004) Expanding role of T-cell costimulators in regulatory T-cell function: recent advances in accessory molecules expressed on both regulatory and nonregulatory T cells. Crit. Rev. Immunol. 24, 251-266.
44. Fontenot, J. D., Gavin, M. A., Rudensky, A. Y. (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4, 330-336.
45. Koesters, S. A., Alimonti, J. B., Wachihi, C., Matu, L., Anzala, O., Kimani, J., Embree, J. E., Plummer, F. A., Fowke, K. R. (2006) IL-7Rα expression on CD4+ T lymphocytes decreases with HIV disease progression and inversely correlates with immune activation. Eur. J. Immunol. 36, 336-344.
46. Marchetti, G., Meroni, L., Molteni, C., Taskaris, G., Gazzola, L., Galli, M., Clerici, M., Moroni, M., Franzetti, F., Gori, A. (2004) IL-7/IL-7 receptor system regulation following IL-2 immunotherapy in HIV-infected patients. Antivir. Ther. 9, 447-452.
47. Mussini, C., Pinti, M., Borghi, V., Nasi, M., Amorico, G., Monterastelli, E., Moretti, L., Troiano, L., Esposito, R., Cossarizza, A. (2002) Features of 'CD4-exploders', HIV-positive patients with an optimal immune reconstitution after potent antiretroviral therapy. AIDS 16, 1609-1616.
48. Carini, C., McLane, M. F., Mayer, K. H., Essex, M. (1994) Dysregulation of interleukin-7 receptor may generate loss of cytotoxic T cell response in human immunodeficiency virus type 1 infection. Eur. J. Immunol. 24, 2927-2934.
49. Colle, J. H., Moreau, J. L., Fontanet, A., Lambotte, O., Joussemet, M., Delfraissy, J. F., Theze, J. (2006) CD127 expression and regulation are altered in the memory CD8 T cells of HIV-infected patients - reversal by highly active anti-retroviral therapy (HAART). Clin. Exp. Immunol. 143, 398-403.
50. Vingerhoets, J., Bisalinkumi, E., Penne, G., Colebunders, R., Bosmans, E., Kestens, L., Vanham, G. (1998) Altered receptor expression and decreased sensitivity of T-cells to the stimulatory cytokines IL-2, IL-7 and IL-12 in HIV infection. Immunol. Lett. 61, 53-61.
51. Sasson, S. C., Zaunders, J. J., Zanetti, G., King, E. M., Merlin, K. M., Smith, D. E., Stanley, K. K., Cooper, D. A., Kelleher, A. D. (2006) Increased plasma interleukin-7 level correlates with decreased CD127 and increased CD132 extracellular expression on T cell subsets in patients with HIV-1 infection. J. Infect. Dis. 193, 505-514.
52. Rethi, B., Fluur, C., Atlas, A., Krzyzowska, M., Mowafi, F., Grutzmeier, S., De Milito, A., Bellocco, R., Falk, K. I., Rajnavolgyi, E., Chiodi, F. (2005) Loss of IL-7Rα is associated with CD4 T-cell depletion, high interleukin-7 levels and CD28 down-regulation in HIV infected patients. AIDS 19, 2077-2086.
53. MacPherson, P. A., Fex, C., Sanchez-Dardon, J., Hawley-Foss, N., Angel, J. B. (2001) Interleukin-7 receptor expression on CD8(+) T cells is reduced in HIV infection and partially restored with effective antiretroviral therapy. J. Acquir. Immune Defic. Syndr. 28, 454-457.
54. Vukmanovic-Stejic, M., Zhang, Y., Cook, J. E., Fletcher, J. M., McQuaid, A., Masters, J. E., Rustin, M. H., Taams, L. S., Beverley, P. C., Macallan, D. C., Akbar, A. N. (2006) Human CD4+ CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. J. Clin. Invest. 116, 2423-2433.
55. Estes, J. D., Li, Q., Reynolds, M. R., Wietgrefe, S., Duan, L., Schacker, T., Picker, L. J., Watkins, D. I., Lifson, J. D., Reilly, C., Carlis, J., Haase, A. T. (2006) Premature induction of an immunosuppressive regulatory T cell response during acute simian immunodeficiency virus infection. J. Infect. Dis. 193, 703-712.
56. Nilsson, J., Boasso, A., Velilla, P. A., Zhang, R., Vaccari, M., Franchini, G., Shearer, G. M., Andersson, J., Chougnet, C. (2006) HIV-1 driven regulatory T cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood 108, 3808-3817.
57. Liu, Z., Hultin, L. E., Cumberland, W. G., Hultin, P., Schmid, I., Matud, J. L., Detels, R., Giorgi, J. V. (1996) Elevated relative fluorescence intensity of CD38 antigen expression on CD8+ T cells is a marker of poor prognosis in HIV infection: results of 6 years of follow-up. Cytometry 26, 1-7.
58. Liu, Z., Cumberland, W. G., Hultin, L. E., Prince, H. E., Detels, R., Giorgi, J. V. (1997) Elevated CD38 antigen expression on CD8+ T cells is a stronger marker for the risk of chronic HIV disease progression to AIDS and death in the Multicenter AIDS Cohort Study than CD4+ cell count, soluble immune activation markers, or combinations of HLA-DR and CD38 expression. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 16, 83-92.
59. Schindler, M., Munch, J., Kutsch, O., Li, H., Santiago, M. L., Bibollet-Ruche, F., Muller-Trutwin, M. C., Novembre, F. J., Peeters, M., Courgnaud, V., Bailes, E., Roques, P., Sodora, D. L., Silvestri, G., Sharp, P. M., Hahn, B. H., Kirchhoff, F. (2006) Nef-mediated suppression of T cell activation was lost in a lentiviral lineage that gave rise to HIV-1. Cell 125, 1055-1067.
60. Ono, M., Yaguchi, H., Ohkura, N., Kitabayashi, I., Nagamura, Y., Nomura, T., Miyachi, Y., Tsukada, T., Sakaguchi, S. (2007) Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature 446, 685-689.
61. Bettelli, E., Dastrange, M., Oukka, M. (2005) Foxp3 interacts with nuclear factor of activated T cells and NF-κ B to repress cytokine gene expression and effector functions of T helper cells. Proc. Natl. Acad. Sci. USA 102, 5138-5143.
62. Wu, Y., Borde, M., Heissmeyer, V., Feuerer, M., Lapan, A. D., Stroud, J. C., Bates, D. L., Guo, L., Han, A., Ziegler, S. F., Mathis, D., Benoist, C., Chen, L., Rao, A. (2006) FOXP3 controls regulatory T cell function through cooperation with NFAT. Cell 126, 375-387.
63. Walker, M. R., Kasprowicz, D. J., Gersuk, V. H., Benard, A., Van Landeghen, M., Buckner, J. H., Ziegler, S. F. (2003) Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25-T cells. J. Clin. Invest. 112, 1437-1443.
64. Tran, D. Q., Ramsey, H., Shevach, E. M. (2007) Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-β dependent but does not confer a regulatory phenotype. Blood 110, 2983-2990.
65. Khattri, R., Cox, T., Yasayko, S. A., Ramsdell, F. (2003) An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol. 4, 337-342.
66. Thornton, A. M., Shevach, E. M. (2000) Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J. Immunol. 164, 183-190.
67. Von Boehmer, H. (2005) Mechanisms of suppression by suppressor T cells. Nat. Immunol. 6, 338-344.