Regulation of antiviral T cell responses by type i interferons

Nature Reviews Immunology

Volumn 15, Issue 4, 2015, Pages 231-242

  Crouse, Josh ^a   Kalinke, Ulrich ^b   Oxenius, Annette ^a  

^a ETH ZURICH   (Switzerland)

^b INSTITUTE OF INFECTION IMMUNOLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; INTERFERON; T LYMPHOCYTE RECEPTOR;

ANTIGEN PRESENTING CELL; CD4+ T LYMPHOCYTE; CELL ADHESION; CELL KILLING; CELL MIGRATION; CELL SURVIVAL; CELLULAR IMMUNITY; CYTOKINE PRODUCTION; DENDRITIC CELL; HUMAN; IMMUNOREGULATION; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE PROLIFERATION; NATURAL KILLER CELL; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; ANIMAL; IMMUNOLOGY; IMMUNOMODULATION; LYMPHOCYTE ACTIVATION; METABOLISM; VIROLOGY; VIRUS INFECTION;

ANIMALS; HUMANS; IMMUNOMODULATION; INTERFERON TYPE I; LYMPHOCYTE ACTIVATION; SIGNAL TRANSDUCTION; T-LYMPHOCYTES; VIRUS DISEASES;

EID: 84925719346     PISSN: 14741733     EISSN: 14741741     Source Type: Journal    
DOI: 10.1038/nri3806     Document Type: Review

References (148)

1. Isaacs, A. & Lindenmann, J. Virus interference. I. The interferon. Proc. R. Soc. Lond. B Biol. Sci. 147, 258-267 (1957).
2. Pestka, S., Krause, C. D. & Walter, M. R. Interferons, interferon-like cytokines, and their receptors. Immunol. Rev. 202, 8-32 (2004).
3. Prokunina-Olsson, L. et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nature Genet. 45, 164-171 (2013).
4. Megjugorac, N. J., Gallagher, G. E. & Gallagher, G. Modulation of human plasmacytoid DC function by IFN-λ1 (IL-29). J. Leukoc. Biol. 86, 1359-1363 (2009).
5. Cavlar, T., Ablasser, A. & Hornung, V. Induction of type I IFNs by intracellular DNA-sensing pathways. Immunol. Cell Biol. 90, 474-482 (2012).
6. Hornung, V., Hartmann, R., Ablasser, A. & Hopfner, K. P. OAS proteins and cGAS: unifying concepts in sensing and responding to cytosolic nucleic acids. Nature Rev. Immunol. 14, 521-528 (2014).
7. Barchet, W. et al. Virus-induced interferon-α production by a dendritic cell subset in the absence of feedback signaling in vivo. J. Exp. Med. 195, 507-516 (2002).
8. Reizis, B., Bunin, A., Ghosh, H. S., Lewis, K. L. & Sisirak, V. Plasmacytoid dendritic cells: recent progress and open questions. Annu. Rev. Immunol. 29, 163-183 (2011).
9. Swiecki, M., Wang, Y., Gilfillan, S. & Colonna, M. Plasmacytoid dendritic cells contribute to systemic but not local antiviral responses to HSV infections. PLoS Pathog. 9, e1003728 (2013).
10. Swiecki, M., Gilfillan, S., Vermi, W., Wang, Y. & Colonna, M. Plasmacytoid dendritic cell ablation impacts early interferon responses and antiviral NK and CD8+ T cell accrual. Immunity 33, 955-966 (2010).
11. Paquette, R. L. et al. Interferon-α and granulocytemacrophage colony-stimulating factor differentiate peripheral blood monocytes into potent antigenpresenting cells. J. Leukoc. Biol. 64, 358-367 (1998).
12. Santini, S. M. et al. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J. Exp. Med. 191, 1777-1788 (2000).
13. Hahm, B., Trifilo, M. J., Zuniga, E. I. & Oldstone, M. B. Viruses evade the immune system through type I interferon-mediated STAT2-dependent, but STAT1-independent, signaling. Immunity 22, 247-257 (2005).
14. Parlato, S. et al. Expression of CCR-7, MIP-3β, and TH-1 chemokines in type I IFN-induced monocytederived dendritic cells: importance for the rapid acquisition of potent migratory and functional activities. Blood 98, 3022-3029 (2001).
15. Rouzaut, A. et al. Dendritic cells adhere to and transmigrate across lymphatic endothelium in response to IFN-α. Eur. J. Immunol. 40, 3054-3063 (2010).
16. Padovan, E., Spagnoli, G. C., Ferrantini, M. & Heberer, M. IFN-α2a induces IP-10/CXCL10 and MIG/CXCL9 production in monocyte-derived dendritic cells and enhances their capacity to attract and stimulate CD8+ effector T cells. J. Leukoc. Biol. 71, 669-676 (2002).
17. Radvanyi, L. G., Banerjee, A., Weir, M. & Messner, H. Low levels of interferon-α induce CD86 (B7.2) expression and accelerates dendritic cell maturation from human peripheral blood mononuclear cells. Scand. J. Immunol. 50, 499-509 (1999).
18. Luft, T. et al. Type I IFNs enhance the terminal differentiation of dendritic cells. J. Immunol. 161, 1947-1953 (1998).
19. Blanco, P., Palucka, A. K., Gill, M., Pascual, V. & Banchereau, J. Induction of dendritic cell differentiation by IFN-α in systemic lupus erythematosus. Science 294, 1540-1543 (2001).
20. Gallucci, S., Lolkema, M. & Matzinger, P. Natural adjuvants: endogenous activators of dendritic cells. Nature Med. 5, 1249-1255 (1999).
21. Montoya, M. et al. Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood 99, 3263-3271 (2002).
22. Longhi, M. P. et al. Dendritic cells require a systemic type I interferon response to mature and induce CD4+ TH1 immunity with poly IC as adjuvant. J. Exp. Med. 206, 1589-1602 (2009).
23. Simmons, D. P. et al. Type I IFN drives a distinctive dendritic cell maturation phenotype that allows continued class II MHC synthesis and antigen processing. J. Immunol. 188, 3116-3126 (2012).
24. Joffre, O. P., Segura, E., Savina, A. & Amigorena, S. Cross-presentation by dendritic cells. Nature Rev. Immunol. 12, 557-569 (2012).
25. Nierkens, S., Tel, J., Janssen, E. & Adema, G. J. Antigen cross-presentation by dendritic cell subsets: one general or all sergeants? Trends Immunol. 34, 361-370 (2013).
26. Le Bon, A. et al. Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon. Nature Immunol. 4, 1009-1015 (2003).
27. Spadaro, F. et al. IFN-α enhances cross-presentation in human dendritic cells by modulating antigen survival, endocytic routing, and processing. Blood 119, 1407-1417 (2012).
28. Savina, A. et al. The small GTPase Rac2 controls phagosomal alkalinization and antigen crosspresentation selectively in CD8+ dendritic cells. Immunity 30, 544-555 (2009).
29. Thomas, C. et al. Structural linkage between ligand discrimination and receptor activation by type I interferons. Cell 146, 621-632 (2011).
30. Garcin, G. et al. Differential activity of type I interferon subtypes for dendritic cell differentiation. PLoS ONE 8, e58465 (2013).
31. Antonelli, L. R. et al. Intranasal Poly-IC treatment exacerbates tuberculosis in mice through the pulmonary recruitment of a pathogen-permissive monocyte/macrophage population. J. Clin. Invest. 120, 1674-1682 (2010).
32. McNab, F. W. et al. TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production. J. Immunol. 191, 1732-1743 (2013).
33. Teijaro, J. R. et al. Persistent LCMV infection is controlled by blockade of type I interferon signaling. Science 340, 207-211 (2013).
34. Wilson, E. B. et al. Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science 340, 202-207 (2013).
35. Wilson, E. B. et al. Emergence of distinct multiarmed immunoregulatory antigen-presenting cells during persistent viral infection. Cell Host Microbe 11, 481-491 (2012).
36. Mattei, F., Schiavoni, G., Belardelli, F. & Tough, D. F. IL-15 is expressed by dendritic cells in response to type I IFN, double-stranded RNA, or lipopolysaccharide and promotes dendritic cell activation. J. Immunol. 167, 1179-1187 (2001).
37. Zhang, X., Sun, S., Hwang, I., Tough, D. F. & Sprent, J. Potent and selective stimulation of memoryphenotype CD8+ T cells in vivo by IL-15. Immunity 8, 591-599 (1998).
38. Nguyen, K. B. et al. Coordinated and distinct roles for IFN-α β, IL-12, and IL-15 regulation of NK cell responses to viral infection. J. Immunol. 169, 4279-4287 (2002).
39. Lucas, M., Schachterle, W., Oberle, K., Aichele, P. & Diefenbach, A. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity 26, 503-517 (2007).
40. Dubois, S., Mariner, J., Waldmann, T. A. & Tagaya, Y. IL-15Rα recycles and presents IL-15 in trans to neighboring cells. Immunity 17, 537-547 (2002).
41. Nguyen, K. B. et al. Critical role for STAT4 activation by type 1 interferons in the interferon-γ response to viral infection. Science 297, 2063-2066 (2002).
42. Swain, S. L., McKinstry, K. K. & Strutt, T. M. Expanding roles for CD4+ T cells in immunity to viruses. Nature Rev. Immunol. 12, 136-148 (2012).
43. Surh, C. D. & Sprent, J. Homeostasis of naive and memory T cells. Immunity 29, 848-862 (2008).
44. Cousens, L. P., Orange, J. S., Su, H. C. & Biron, C. A. Interferon-α/β inhibition of interleukin 12 and interferon-γ production in vitro and endogenously during viral infection. Proc. Natl Acad. Sci. USA 94, 634-639 (1997).
45. Byrnes, A. A. et al. Type I interferons and IL-12: convergence and cross-regulation among mediators of cellular immunity. Eur. J. Immunol. 31, 2026-2034 (2001).
46. Biron, C. A., Sonnenfeld, G. & Welsh, R. M. Interferon induces natural killer cell blastogenesis in vivo. J. Leukoc. Biol. 35, 31-37 (1984).
47. Gidlund, M., Orn, A., Wigzell, H., Senik, A. & Gresser, I. Enhanced NK cell activity in mice injected with interferon and interferon inducers. Nature 273, 759-761 (1978).
48. Lee, C. K. et al. Distinct requirements for IFNs and STAT1 in NK cell function. J. Immunol. 165, 3571-3577 (2000).
49. Jost, S. & Altfeld, M. Control of human viral infections by natural killer cells. Annu. Rev. Immunol. 31, 163-194 (2013).
50. Scott, P. IFN-γ modulates the early development of TH1 and TH2 responses in a murine model of cutaneous leishmaniasis. J. Immunol. 147, 3149-3155 (1991).
51. Lighvani, A. A. et al. T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells. Proc. Natl Acad. Sci. USA 98, 15137-15142 (2001).
52. Crome, S. Q., Lang, P. A., Lang, K. S. & Ohashi, P. S. Natural killer cells regulate diverse T cell responses. Trends Immunol. 34, 342-349 (2013).
53. Crouse, J., Xu, H. C., Lang, P. A. & Oxenius, A. NK cells regulating T cell responses: mechanisms and outcome. Trends Immunol. 36, 49-58 (2014).
54. Lu, L. et al. Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway. Immunity 26, 593-604 (2007).
55. Waggoner, S. N., Taniguchi, R. T., Mathew, P. A., Kumar, V. & Welsh, R. M. Absence of mouse 2B4 promotes NK cell-mediated killing of activated CD8+ T cells, leading to prolonged viral persistence and altered pathogenesis. J. Clin. Invest. 120, 1925-1938 (2010).
56. Xu, H. C. et al. Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity. Immunity 40, 949-960 (2014).
57. Rabinovich, B. A. et al. Activated, but not resting, T cells can be recognized and killed by syngeneic NK cells. J. Immunol. 170, 3572-3576 (2003).
58. Cerboni, C. et al. Antigen-activated human T lymphocytes express cell-surface NKG2D ligands via an ATM/ATR-dependent mechanism and become susceptible to autologous NK-cell lysis. Blood 110, 606-615 (2007).
59. Soderquest, K. et al. Cutting edge: CD8+ T cell priming in the absence of NK cells leads to enhanced memory responses. J. Immunol. 186, 3304-3308 (2011).
60. Crouse, J. et al. Type I interferons protect T cells against NK cell attack mediated by the activating receptor NCR1. Immunity 40, 961-973 (2014).
61. Peppa, D. et al. Up-regulation of a death receptor renders antiviral T cells susceptible to NK cellmediated deletion. J. Exp. Med. 210, 99-114 (2013).
62. Sadler, A. J. & Williams, B. R. Interferon-inducible antiviral effectors. Nature Rev. Immunol. 8, 559-568 (2008).
63. Honke, N. et al. Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus. Nature Immunol. 13, 51-57 (2012).
64. Wherry, E. J., Blattman, J. N., Murali-Krishna, K., van der Most, R. & Ahmed, R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J. Virol. 77, 4911-4927 (2003).
65. Richter, K., Brocker, T. & Oxenius, A. Antigen amount dictates CD8+ T-cell exhaustion during chronic viral infection irrespective of the type of antigen presenting cell. Eur. J. Immunol. 42, 2290-2304 (2012).
66. Mueller, S. N. & Ahmed, R. High antigen levels are the cause of T cell exhaustion during chronic viral infection. Proc. Natl Acad. Sci. USA 106, 8623-8628 (2009).
67. Streeck, H. et al. Antigen load and viral sequence diversification determine the functional profile of HIV-1-specific CD8+ T cells. PLoS Med. 5, e100 (2008).
68. van Boxel-Dezaire, A. H., Rani, M. R. & Stark, G. R. Complex modulation of cell type-specific signaling in response to type I interferons. Immunity 25, 361-372 (2006).
69. Brierley, M. M. & Fish, E. N. Stats: multifaceted regulators of transcription. J. Interferon Cytokine Res. 25, 733-744 (2005).
70. Platanias, L. C. Mechanisms of type-I-and type-IIinterferon-mediated signalling. Nature Rev. Immunol. 5, 375-386 (2005).
71. Tanabe, Y. et al. Cutting edge: role of STAT1, STAT3, and STAT5 in IFN-α β responses in T lymphocytes. J. Immunol. 174, 609-613 (2005).
72. Gimeno, R., Lee, C. K., Schindler, C. & Levy, D. E. Stat1 and Stat2 but not Stat3 arbitrate contradictory growth signals elicited by α/β interferon in T lymphocytes. Mol. Cell. Biol. 25, 5456-5465 (2005).
73. Van De Wiele, C. J. et al. Loss of interferon-induced Stat1 phosphorylation in activated T cells. J. Interferon Cytokine Res. 24, 169-178 (2004).
74. Curtsinger, J. M., Valenzuela, J. O., Agarwal, P., Lins, D. & Mescher, M. F. Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. J. Immunol. 174, 4465-4469 (2005).
75. Garcia-Sastre, A. & Biron, C. A. Type 1 interferons and the virus-host relationship: a lesson in detente. Science 312, 879-882 (2006).
76. Gil, M. P., Salomon, R., Louten, J. & Biron, C. A. Modulation of STAT1 protein levels: a mechanism shaping CD8 T-cell responses in vivo. Blood 107, 987-993 (2006).
77. Curtsinger, J. M., Lins, D. C. & Mescher, M. F. Signal 3 determines tolerance versus full activation of naive CD8 T cells: dissociating proliferation and development of effector function. J. Exp. Med. 197, 1141-1151 (2003).
78. Curtsinger, J. M., Johnson, C. M. & Mescher, M. F. CD8 T cell clonal expansion and development of effector function require prolonged exposure to antigen, costimulation, and signal 3 cytokine. J. Immunol. 171, 5165-5171 (2003).
79. Hervas-Stubbs, S. et al. Effects of IFN-α as a signal-3 cytokine on human naive and antigen-experienced CD8+ T cells. Eur. J. Immunol. 40, 3389-3402 (2010).
80. Cha, L., de Jong, E., French, M. A. & Fernandez, S. IFN-α exerts opposing effects on activation-induced & IL-7-induced proliferation of T cells that may impair homeostatic maintenance of CD4+ T cell numbers in reated HIV infection. J. Immunol. 193, 2178-2186 (2014).
81. Matikainen, S. et al. Interferon-α activates multiple STAT proteins and upregulates proliferationassociated IL-2Rα, c-myc, and pim-1 genes in human T cells. Blood 93, 1980-1991 (1999).
82. Pilling, D. et al. Interferon-β mediates stromal cell rescue of T cells from apoptosis. Eur. J. Immunol. 29, 1041-1050 (1999).
83. Marrack, P., Kappler, J. & Mitchell, T. Type I interferons keep activated T cells alive. J. Exp. Med. 189, 521-530 (1999).
84. Kolumam, G. A., Thomas, S., Thompson, L. J., Sprent, J. & Murali-Krishna, K. Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection. J. Exp. Med. 202, 637-650 (2005).
85. Aichele, P. et al. CD8 T cells specific for lymphocytic choriomeningitis virus require type I IFN receptor for clonal expansion. J. Immunol. 176, 4525-4529 (2006).
86. Thompson, L. J., Kolumam, G. A., Thomas, S. & Murali-Krishna, K. Innate inflammatory signals induced by various pathogens differentially dictate the IFN-I dependence of CD8 T cells for clonal expansion and memory formation. J. Immunol. 177, 1746-1754 (2006).
87. Havenar-Daughton, C., Kolumam, G. A. & Murali-Krishna, K. Cutting edge: the direct action of type I IFN on CD4 T cells is critical for sustaining clonal expansion in response to a viral but not a bacterial infection. J. Immunol. 176, 3315-3319 (2006).
88. Keppler, S. J., Rosenits, K., Koegl, T., Vucikuja, S. & Aichele, P. Signal 3 cytokines as modulators of primary immune responses during infections: the interplay of type I IFN and IL-12 in CD8 T cell responses. PLoS ONE 7, e40865 (2012).
89. Wiesel, M. et al. Type-I IFN drives the differentiation of short-lived effector CD8+ T cells in vivo. Eur. J. Immunol. 42, 320-329 (2012).
90. Frenz, T. et al. Concomitant type I IFN receptortriggering of T cells and of DC is required to promote maximal modified vaccinia virus Ankara-induced T-cell expansion. Eur. J. Immunol. 40, 2769-2777 (2010).
91. Keppler, S. J. & Aichele, P. Signal 3 requirement for memory CD8+ T-cell activation is determined by the infectious pathogen. Eur. J. Immunol. 41, 3176-3186 (2011).
92. Le Bon, A. et al. Direct stimulation of T cells by type I IFN enhances the CD8+ T cell response during crosspriming. J. Immunol. 176, 4682-4689 (2006).
93. Van Uden, J. H., Tran, C. H., Carson, D. A. & Raz, E. Type I interferon is required to mount an adaptive response to immunostimulatory DNA. Eur. J. Immunol. 31, 3281-3290 (2001).
94. Pham, N. L., Badovinac, V. P. & Harty, J. T. Differential role of 'Signal 3' inflammatory cytokines in regulating CD8 T cell expansion and differentiation in vivo. Front. Immunol. 2, 4 (2011).
95. Starbeck-Miller, G. R., Xue, H. H. & Harty, J. T. IL-12 and type I interferon prolong the division of activated CD8 T cells by maintaining high-affinity IL-2 signaling in vivo. J. Exp. Med. 211, 105-120 (2014).
96. Xiao, Z., Casey, K. A., Jameson, S. C., Curtsinger, J. M. & Mescher, M. F. Programming for CD8 T cell memory development requires IL-12 or type I IFN. J. Immunol. 182, 2786-2794 (2009).
97. Nguyen, K. B. et al. Interferon-α/β-mediated inhibition and promotion of interferon-γ: STAT1 resolves a paradox. Nature Immunol. 1, 70-76 (2000).
98. Gil, M. P. et al. Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function. Blood 120, 3718-3728 (2012).
99. Agarwal, P. et al. Gene regulation and chromatin remodeling by IL-12 and type I IFN in programming for CD8 T cell effector function and memory. J. Immunol. 183, 1695-1704 (2009).
100. Keppler, S. J., Theil, K., Vucikuja, S. & Aichele, P. Effector T-cell differentiation during viral and bacterial infections: role of direct IL-12 signals for cell fate decision of CD8+ T cells. Eur. J. Immunol. 39, 1774-1783 (2009).
101. Wiesel, M., Kratky, W. & Oxenius, A. Type I IFN substitutes for T cell help during viral infections. J. Immunol. 186, 754-763 (2011).
102. Kalia, V. et al. Prolonged interleukin-2Rα expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo. Immunity 32, 91-103 (2010).
103. Pipkin, M. E. et al. Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity 32, 79-90 (2010).
104. Gerner, M. Y., Heltemes-Harris, L. M., Fife, B. T. & Mescher, M. F. Cutting edge: IL-12 and type I IFN differentially program CD8 T cells for programmed death 1 re-expression levels and tumor control. J. Immunol. 191, 1011-1015 (2013).
105. Yamane, H. & Paul, W. E. Cytokines of the γc family control CD4+ T cell differentiation and function. Nature Immunol. 13, 1037-1044 (2012).
106. Brinkmann, V., Geiger, T., Alkan, S. & Heusser, C. H. Interferon-α increases the frequency of interferon γ-producing human CD4+ T cells. J. Exp. Med. 178, 1655-1663 (1993).
107. Athie-Morales, V., Smits, H. H., Cantrell, D. A. & Hilkens, C. M. Sustained IL-12 signaling is required for TH1 development. J. Immunol. 172, 61-69 (2004).
108. Ramos, H. J., Davis, A. M., George, T. C. & Farrar, J. D. IFN-α is not sufficient to drive TH1 development due to lack of stable T-bet expression. J. Immunol. 179, 3792-3803 (2007).
109. Persky, M. E., Murphy, K. M. & Farrar, J. D. IL-12, but not IFN-α, promotes STAT4 activation and TH1 development in murine CD4+ T cells expressing a chimeric murine/human Stat2 gene. J. Immunol. 174, 294-301 (2005).
110. Rogge, L. et al. The role of Stat4 in species-specific regulation of TH cell development by type I IFNs. J. Immunol. 161, 6567-6574 (1998).
111. Nurieva, R. I. et al. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 29, 138-149 (2008).
112. Ma, C. S. et al. Functional STAT3 deficiency compromises the generation of human T follicular helper cells. Blood 119, 3997-4008 (2012).
113. Ray, J. P. et al. Transcription factor STAT3 and type I interferons are corepressive insulators for differentiation of follicular helper and T helper 1 cells. Immunity 40, 367-377 (2014).
114. Oestreich, K. J., Mohn, S. E. & Weinmann, A. S. Molecular mechanisms that control the expression and activity of Bcl-6 in TH1 cells to regulate flexibility with a TFH-like gene profile. Nature Immunol. 13, 405-411 (2012).
115. Crotty, S. Follicular helper CD4 T cells (TFH). Annu. Rev. Immunol. 29, 621-663 (2011).
116. Nakayamada, S. et al. Type I IFN induces binding of STAT1 to Bcl6: divergent roles of STAT family transcription factors in the T follicular helper cell genetic program. J. Immunol. 192, 2156-2166 (2014).
117. Srivastava, S., Koch, M. A., Pepper, M. & Campbell, D. J. Type I interferons directly inhibit regulatory T cells to allow optimal antiviral T cell responses during acute LCMV infection. J. Exp. Med. 211, 961-974 (2014).
118. Hansson, M., Kiessling, R., Andersson, B. & Welsh, R. M. Effect of interferon and interferon inducers on the NK sensitivity of normal mouse thymocytes. J. Immunol. 125, 2225-2231 (1980).
119. Kamphuis, E., Junt, T., Waibler, Z., Forster, R. & Kalinke, U. Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia. Blood 108, 3253-3261 (2006).
120. Shiow, L. R. et al. CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 440, 540-544 (2006).
121. Schulz, O. et al. Hypertrophy of infected Peyer's patches arises from global, interferon-receptor, and CD69-independent shutdown of lymphocyte egress. Mucosal Immunol. 7, 892-904 (2014).
122. Avraamides, G. et al. IFN-α2 induces leukocyte integrin redistribution, increased adhesion, and migration. J. Interferon Cytokine Res. 27, 291-303 (2007).
123. Dondi, E., Rogge, L., Lutfalla, G., Uze, G. & Pellegrini, S. Down-modulation of responses to type I IFN upon T cell activation. J. Immunol. 170, 749-756 (2003).
124. Sun, S., Zhang, X., Tough, D. F. & Sprent, J. Type I interferon-mediated stimulation of T cells by CpG DNA. J. Exp. Med. 188, 2335-2342 (1998).
125. Bromberg, J. F., Horvath, C. M., Wen, Z., Schreiber, R. D. & Darnell, J. E. Jr. Transcriptionally active Stat1 is required for the antiproliferative effects of both interferon α and interferon γ. Proc. Natl Acad. Sci. USA 93, 7673-7678 (1996).
126. Petricoin, E. F. et al. Antiproliferative action of interferon-α requires components of T-cell-receptor signalling. Nature 390, 629-632 (1997).
127. Terawaki, S. et al. IFN-α directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity. J. Immunol. 186, 2772-2779 (2011).
128. Herbeuval, J. P. et al. Regulation of TNF-related apoptosis-inducing ligand on primary CD4+ T cells by HIV-1: role of type I IFN-producing plasmacytoid dendritic cells. Proc. Natl Acad. Sci. USA 102, 13974-13979 (2005).
129. Kaser, A., Nagata, S. & Tilg, H. Interferon-α augments activation-induced T cell death by upregulation of Fas (CD95/APO-1) and Fas ligand expression. Cytokine 11, 736-743 (1999).
130. Fraietta, J. A. et al. Type I interferon upregulates Bak and contributes to T cell loss during human immunodeficiency virus (HIV) infection. PLoS Pathog. 9, e1003658 (2013).
131. Zella, D. et al. IFN-α 2b reduces IL-2 production and IL-2 receptor function in primary CD4+ T cells. J. Immunol. 164, 2296-2302 (2000).
132. Bahl, K., Huebner, A., Davis, R. J. & Welsh, R. M. Analysis of apoptosis of memory T cells and dendritic cells during the early stages of viral infection or exposure to toll-like receptor agonists. J. Virol. 84, 4866-4877 (2010).
133. McNally, J. M. et al. Attrition of bystander CD8 T cells during virus-induced T-cell and interferon responses. J. Virol. 75, 5965-5976 (2001).
134. Bahl, K. et al. IFN-induced attrition of CD8 T cells in the presence or absence of cognate antigen during the early stages of viral infections. J. Immunol. 176, 4284-4295 (2006).
135. Jiang, J., Lau, L. L. & Shen, H. Selective depletion of nonspecific T cells during the early stage of immune responses to infection. J. Immunol. 171, 4352-4358 (2003).
136. Marshall, H. D., Prince, A. L., Berg, L. J. & Welsh, R. M. IFN-α β and self-MHC divert CD8 T cells into a distinct differentiation pathway characterized by rapid acquisition of effector functions. J. Immunol. 185, 1419-1428 (2010).
137. Marshall, H. D., Urban, S. L. & Welsh, R. M. Virus-induced transient immune suppression and the inhibition of T cell proliferation by type I interferon. J. Virol. 85, 5929-5939 (2011).
138. Urban, S. L. & Welsh, R. M. Out-of-sequence signal 3 as a mechanism for virus-induced immune suppression of CD8 T cell responses. PLoS Pathog. 10, e1004357 (2014).
139. Piganis, R. A. et al. Suppressor of cytokine signaling (SOCS) 1 inhibits type I interferon (IFN) signaling via the interferon α receptor (IFNAR1)-associated tyrosine kinase Tyk2. J. Biol. Chem. 286, 33811-33818 (2011).
140. Manches, O. & Bhardwaj, N. Resolution of immune activation defines nonpathogenic SIV infection. J. Clin. Invest. 119, 3512-3515 (2009).
141. Hosmalin, A. & Lebon, P. Type I interferon production in HIV-infected patients. J. Leukoc. Biol. 80, 984-993 (2006).
142. Sandler, N. G. et al. Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature 511, 601-605 (2014).
143. Baccala, R. et al. Type I interferon is a therapeutic target for virus-induced lethal vascular damage. Proc. Natl Acad. Sci. USA 111, 8925-8930 (2014).
144. Wang, Y. et al. Timing and magnitude of type I interferon responses by distinct sensors impact CD8 T cell exhaustion and chronic viral infection. Cell Host Microbe 11, 631-642 (2012).
145. Lee, M. S., Park, C. H., Jeong, Y. H., Kim, Y. J. & Ha, S. J. Negative regulation of type I IFN expression by OASL1 permits chronic viral infection and CD8+ T-cell exhaustion. PLoS Pathog. 9, e1003478 (2013).
146. Vezys, V. et al. Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection. J. Exp. Med. 203, 2263-2269 (2006).
147. Osokine, I. et al. Type I interferon suppresses de novo virus-specific CD4 TH1 immunity during an established persistent viral infection. Proc. Natl Acad. Sci. USA 111, 7409-7414 (2014).
148. Stelekati, E. et al. Bystander chronic infection negatively impacts development of CD8+ T cell memory. Immunity 40, 801-813 (2014).