Cutting Edge: Antigen-Independent CD8 T Cell Proliferation

Recent 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.

[1]  S. Jameson,et al.  Interleukin-7 mediates the homeostasis of naïve and memory CD8 T cells in vivo , 2000, Nature Immunology.

[2]  D. Busch,et al.  MHC class I antigen processing of Listeria monocytogenes proteins: implications for dominant and subdominant CTL responses , 1997, Immunological reviews.

[3]  Sanjeev Kumar,et al.  Relative roles of T‐cell receptor ligands and interleukin‐2 in driving T‐cell proliferation , 1999, Journal of cellular biochemistry.

[4]  Laurence Zitvogel,et al.  Molecular Characterization of Dendritic Cell-Derived Exosomes , 1999, The Journal of cell biology.

[5]  David Gray,et al.  Immunological Memory and Protective Immunity: Understanding Their Relation , 1996, Science.

[6]  Kendall A. Smith,et al.  Interleukin-2: inception, impact, and implications. , 1988, Science.

[7]  D. Busch,et al.  Processing of Listeria monocytogenes antigens and the in vivo T‐cell response to bacterial infection , 1999, Immunological reviews.

[8]  J. Altman,et al.  Persistence of memory CD8 T cells in MHC class I-deficient mice. , 1999, Science.

[9]  M. Eichelberger,et al.  Roles of alpha beta and gamma delta T cell subsets in viral immunity. , 1992, Annual review of immunology.

[10]  D. Busch,et al.  Coordinate regulation of complex T cell populations responding to bacterial infection. , 1998, Immunity.

[11]  P. Marrack,et al.  Control of homeostasis of CD8+ memory T cells by opposing cytokines. , 2000, Science.

[12]  J. Sprent,et al.  The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. , 1999, Immunity.

[13]  M. Bevan,et al.  Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. , 1998, Immunity.

[14]  A. Lanzavecchia,et al.  The duration of antigenic stimulation determines the fate of naive and effector T cells. , 1998, Immunity.

[15]  D. Moskophidis,et al.  Enumeration of single IFN-gamma-producing cells in mice during viral and bacterial infection. , 1989, Journal of immunology.

[16]  M. Bevan,et al.  Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts. , 1999, Immunity.

[17]  Eric G. Pamer,et al.  Early Programming of T Cell Populations Responding to Bacterial Infection1 , 2000, The Journal of Immunology.

[18]  R. Grant,et al.  Increased production of IL-7 accompanies HIV-1–mediated T-cell depletion: implications for T-cell homeostasis , 2001, Nature Medicine.

[19]  E. Pamer,et al.  Effect of antigen-processing efficiency on in vivo T cell response magnitudes. , 1998, Journal of immunology.

[20]  M. Kaplan,et al.  Stat Proteins Control Lymphocyte Proliferation by Regulating p27Kip1 Expression , 1998, Molecular and Cellular Biology.

[21]  J. Sprent,et al.  Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. , 1998, Immunity.

[22]  L. Appleman,et al.  CD28 Costimulation Mediates T Cell Expansion Via IL-2-Independent and IL-2-Dependent Regulation of Cell Cycle Progression1 , 2000, The Journal of Immunology.

[23]  T. Strom,et al.  IL-15 and IL-2: a matter of life and death for T cells in vivo , 2001, Nature Medicine.

[24]  E. Pamer,et al.  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 , 1997, The Journal of experimental medicine.

[25]  S. Meuer,et al.  T cell receptor triggering induces responsiveness to interleukin 1 and interleukin 2 but does not lead to T cell proliferation. , 1986, Journal of immunology.

[26]  R. Medema,et al.  CD28 induces cell cycle progression by IL‐2‐independent down‐regulation of p27kip1 expression in human peripheral T lymphocytes , 1999, European journal of immunology.

[27]  J. Harty,et al.  Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma. , 2000, Science.

[28]  D. Busch,et al.  T lymphocyte dynamics during Listeria monocytogenes infection. , 1999, Immunology letters.

[29]  D. Busch,et al.  Differing Roles of Inflammation and Antigen in T Cell Proliferation and Memory Generation1 , 2000, The Journal of Immunology.

[30]  J. Altman,et al.  Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. , 1998, Immunity.