Cutting Edge: Antigen-Independent CD8 T Cell Proliferation

Journal of Immunology - Tập 166 Số 10 - Trang 5864-5868 - 2001
Phillip Wong1, Eric G. Pamer2
1Infectious Diseases Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
2Infectious Diseases Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021

Tóm tắt

AbstractRecent analyses of CD8 T cell responses to Listeria monocytogenes infection demonstrate that the duration of in vivo T cell proliferation is not determined by the amount or duration of Ag presentation. However, the extent to which T lymphocytes are capable of proliferating in the absence of Ag is unknown. Herein we demonstrate that CD8 T lymphocytes undergo up to eight rounds of proliferation in the absence of Ag following transient, 2.5-h in vitro antigenic stimulation. Ag-independent expansion of CD8 T cells is driven by IL-2 and is further augmented by IL-7 or IL-15. These experiments clearly demonstrate that CD8 T cells undergo prolonged proliferation following transient Ag exposure and support the notion that in vivo CD8 T cell expansion following infection can be uncoupled from Ag presentation.

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Tài liệu tham khảo

Ahmed, R., D. Gray. 1996. Immunological memory and protective immunity: understanding their relation. Science 272: 54

Gessner, A., D. Moskophidis, F. Lehmann-Grube. 1989. Enumeration of single IFN-γ-producing cells in mice during viral and bacterial infection. J. Immunol. 142: 1293

Doherty, P. C., W. Allan, M. Eichelberger, S. R. Carding. 1992. Roles of αβ and γδ T cell subsets in viral immunity. Annu. Rev. Immunol. 10: 123

Busch, D. H., K. Kerksiek, E. G. Pamer. 1999. Processing of Listeria monocytogenes antigens and the in vivo T-cell response to bacterial infection. Immunol. Rev. 172: 163

Busch, D. H., E. G. Pamer. 1999. T lymphocyte dynamics during Listeria monocytogenes infection. Immunol. Lett. 65: 93

Busch, D. H., I. M. Pilip, S. Vijh, E. G. Pamer. 1998. Coordinate regulation of complex T cell populations responding to bacterial infection. Immunity 8: 353

Pamer, E. G., A. J. Sijts, M. S. Villanueva, D. H. Busch, S. Vijh. 1997. MHC class I antigen processing of Listeria monocytogenes proteins: implications for dominant and subdominant CTL responses. Immunol. Rev. 158: 129

Mercado, R., S. Vijh, S. E. Allen, K. Kerksiek, I. M. Pilip, E. G. Pamer. 2000. Early programming of T cell populations responding to bacterial infection. J. Immunol. 165: 6833

Sijts, A. J., E. G. Pamer. 1997. Enhanced intracellular dissociation of major histocompatibility complex class I-associated peptides: a mechanism for optimizing the spectrum of cell surface-presented cytotoxic T lymphocyte epitopes. J. Exp. Med. 185: 1403

Thery, C., A. Regnault, J. Garin, J. Wolfers, L. Zitvogel, P. Ricciardi-Castagnoli, G. Raposo, S. Amigorena. 1999. Molecular characterization of dendritic cell-derived exosomes: selective accumulation of the heat shock protein hsc73. J. Cell Biol. 147: 599

Ku, C. C., M. Murakami, A. Sakamoto, J. Kappler, P. Marrack. 2000. Control of homeostasis of CD8+ memory T cells by opposing cytokines. Science 288: 675

Schluns, K. S., W. C. Kieper, S. C. Jameson, L. Lefrancois. 2000. Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat. Immunol. 1: 426

Napolitano, L. A., R. M. Grant, S. G. Deeks, D. Schmidt, S. C. De Rosa, L. A. Herzenberg, B. G. Herndier, J. Andersson, J. M. McCune. 2001. Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis. Nat. Med. 7: 73

Zhang, X., S. Sun, I. Hwang, D. F. Tough, J. Sprent. 1998. Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 8: 591

Vijh, S., I. M. Pilip, E. G. Pamer. 1998. Effect of antigen-processing efficiency on in vivo T cell response magnitudes. J. Immunol. 160: 3971

Butz, E. A., M. J. Bevan. 1998. Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. Immunity 8: 167

Murali-Krishna, K., J. D. Altman, M. Suresh, D. J. Sourdive, A. J. Zajac, J. D. Miller, J. Slansky, R. Ahmed. 1998. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 8: 177

Goldrath, A. W., M. J. Bevan. 1999. Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts. Immunity 11: 183

Ernst, B., D. S. Lee, J. M. Chang, J. Sprent, C. D. Surh. 1999. The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity 11: 173

Murali-Krishna, K., L. L. Lau, S. Sambhara, F. Lemonnier, J. Altman, R. Ahmed. 1999. Persistence of memory CD8 T cells in MHC class I-deficient mice. Science 286: 1377

Iezzi, G., K. Karjalainen, A. Lanzavecchia. 1998. The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity 8: 89

Kaplan, M. H., C. Daniel, U. Schindler, M. J. Grusby. 1998. Stat proteins control lymphocyte proliferation by regulating p27Kip1 expression. Mol. Cell Biol. 18: 1996

Smith, K. A.. 1988. Interleukin-2: inception, impact, and implications. Science 240: 1169

Meur, S. C., K. H. M. Buschenfelde. 1986. T cell receptor triggering induces responsiveness to interleukin 1 and interleukin 2 but does not lead to proliferation. J. Immunol. 136: 4106

Chakrabarti, R., S. Kumar. 1999. Relative roles of T-cell receptor ligands and interleukin-2 in driving T-cell proliferation. J. Cell. Biochem. 76: 37

Li, X. C., G. Demirci, S. Ferrari-Lacraz, C. Groves, A. Coyle, T. R. Malek, T. B. Strom. 2001. IL-15 and IL-2: a matter of life and death for T cells in vivo. Nat. Med. 7: 114

Busch, D. H., K. M. Kerksiek, E. G. Pamer. 2000. Differing roles of inflammation and antigen in T cell proliferation and memory generation. J. Immunol. 164: 4063

Appleman, L. J., A. Berezovskaya, I. Grass, V. A. Boussiotis. 2000. CD28 costimulation mediates T cell expansion via IL-2-independent and IL-2-dependent regulation of cell cycle progression. J. Immunol. 164: 144

Boonen, G. J., A. M. van Dijk, L. F. Verdonck, R. A. van Lier, G. Rijksen, R. H. Medema. 1999. CD28 induces cell cycle progression by IL-2-independent down-regulation of p27kip1 expression in human peripheral T lymphocytes. Eur. J. Immunol. 29: 789

Badovinac, V. P., A. R. Tvinnereim, J. T. Harty. 2000. Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-γ. Science 290: 1354