CD8+ T cell contraction is controlled by early inflammation

Pathogen-specific CD8+ T cells expand in number after infection and then their numbers invariably contract by 90–95%, leaving a stable memory cell pool. The chief features of this response are programmed early after infection; however, the factors regulating contraction are mostly undefined. Here we show that antibiotic treatment before Listeria monocytogenes infection induced numbers of protective memory CD8+ T cells similar to those in control infected mice, by a pathway without contraction. The absence of contraction correlated with decreased early inflammation and interferon-γ production and an increased fraction of CD8+ T cells expressing the interleukin 7 receptor at the peak of the response. Thus, contraction is controlled by early inflammation but is not essential for the generation of protective memory CD8+ T cells after infection.

[1]  E. Wherry,et al.  Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells , 2003, Nature Immunology.

[2]  M. Bachmann,et al.  Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection , 1999, European journal of immunology.

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

[4]  E. Pamer,et al.  Precise prediction of a dominant class I MHC-restricted epitope of Listeria monocytogenes , 1991, Nature.

[5]  J. Harty,et al.  Viral infection results in massive CD8+ T cell expansion and mortality in vaccinated perforin-deficient mice. , 2003, Immunity.

[6]  E. Wherry,et al.  Vaccines: Effector and memory T-cell differentiation: implications for vaccine development , 2002, Nature Reviews Immunology.

[7]  Peter C. Doherty,et al.  Virus-specific CD8+ T-cell memory determined by clonal burst size , 1994, Nature.

[8]  M. Bevan,et al.  Specific immunity to Listeria monocytogenes in the absence of IFN gamma. , 1995, Immunity.

[9]  Stephen C. Jameson,et al.  Maintaining the norm: T-cell homeostasis , 2002, Nature Reviews Immunology.

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

[11]  J. Harty,et al.  Programmed contraction of CD8+ T cells after infection , 2002, Nature Immunology.

[12]  Antonio Lanzavecchia,et al.  Central memory and effector memory T cell subsets: function, generation, and maintenance. , 2004, Annual review of immunology.

[13]  J. Harty,et al.  CD8+ T cell effector mechanisms in resistance to infection. , 2000, Annual review of immunology.

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

[15]  C. Benoist,et al.  Cytokine Requirements for Acute and Basal Homeostatic Proliferation of Naive and Memory CD8+ T Cells , 2002, The Journal of experimental medicine.

[16]  J. Theriot,et al.  Expression and phosphorylation of the Listeria monocytogenes ActA protein in mammalian cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

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

[18]  Dirk Homann,et al.  Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory , 2001, Nature Medicine.

[19]  J. Opferman,et al.  Linear differentiation of cytotoxic effectors into memory T lymphocytes. , 1999, Science.

[20]  L. Lefrançois,et al.  Cutting Edge: Requirement for IL-15 in the Generation of Primary and Memory Antigen-Specific CD8 T Cells1 , 2002, The Journal of Immunology.

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

[22]  Peter Jensen,et al.  CD8αα-Mediated Survival and Differentiation of CD8 Memory T Cell Precursors , 2004, Science.

[23]  J. Sidney,et al.  Analysis of cytotoxic T cell responses to dominant and subdominant epitopes during acute and chronic lymphocytic choriomeningitis virus infection. , 1996, Journal of immunology.

[24]  E. Wherry,et al.  Interleukin 15 Is Required for Proliferative Renewal of Virus-specific Memory CD8 T Cells , 2002, The Journal of experimental medicine.

[25]  A. Krieg CpG motifs: the active ingredient in bacterial extracts? , 2003, Nature Medicine.

[26]  A. Zajac,et al.  Ablation of CD8 and CD4 T Cell Responses by High Viral Loads1 , 2003, The Journal of Immunology.

[27]  Eric G. Pamer,et al.  Cutting Edge: Antigen-Independent CD8 T Cell Proliferation , 2001, The Journal of Immunology.

[28]  P. Marrack,et al.  Interleukin 4 (IL-4) or IL-7 Prevents the Death of Resting T Cells: Stat6 Is Probably Not Required for the Effect of IL-4 , 1997, The Journal of experimental medicine.

[29]  Susan M. Kaech,et al.  Memory CD8+ T cell differentiation: initial antigen encounter triggers a developmental program in naïve cells , 2001, Nature Immunology.

[30]  Stephen P. Schoenberger,et al.  Naïve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation , 2001, Nature Immunology.

[31]  R. Ahmed,et al.  Similarities and differences in CD4+ and CD8+ effector and memory T cell generation , 2003, Nature Immunology.

[32]  J. Sprent,et al.  Overexpression of Interleukin (IL)-7 Leads to IL-15–independent Generation of Memory Phenotype CD8+ T Cells , 2002, The Journal of experimental medicine.

[33]  Hao Shen,et al.  Cutting Edge: CD4 and CD8 T Cells Are Intrinsically Different in Their Proliferative Responses1 , 2002, The Journal of Immunology.

[34]  P. Berche,et al.  Immunologic consequences of antibiotic-induced abridgement of bacterial infection: effect on generation and loss of protective T cells and level of immunologic memory. , 1981, Journal of immunology.

[35]  A. Zajac,et al.  Ablation of CD 8 and CD 4 T Cell Responses by High Viral Loads 1 , 2002 .

[36]  J. Harty,et al.  Intracellular staining for TNF and IFN-gamma detects different frequencies of antigen-specific CD8(+) T cells. , 2000, Journal of immunological methods.

[37]  Susan M. Kaech,et al.  Molecular and Functional Profiling of Memory CD8 T Cell Differentiation , 2002, Cell.

[38]  J. Sprent,et al.  T Cell Death and Memory , 2001, Science.

[39]  J. Harty,et al.  Influence of effector molecules on the CD8(+) T cell response to infection. , 2002, Current opinion in immunology.

[40]  Rustom Antia,et al.  Lineage relationship and protective immunity of memory CD8 T cell subsets , 2003, Nature Immunology.

[41]  Leo Lefrançois,et al.  Cytokine control of memory T-cell development and survival , 2003, Nature Reviews Immunology.

[42]  C. Thompson,et al.  Homeostatic control of lymphocyte survival: potential origins and implications , 2002, Nature Immunology.

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

[44]  Henrique Veiga-Fernandes,et al.  Response of naïve and memory CD8+ T cells to antigen stimulation in vivo , 2000, Nature Immunology.

[45]  Joshy Jacob,et al.  Modelling T-cell memory by genetic marking of memory T cells in vivo , 1999, Nature.

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

[47]  E. Wherry,et al.  Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment , 2003, Journal of Virology.

[48]  J. Sprent,et al.  T cell memory. , 2003, Annual review of immunology.

[49]  J. Sprent,et al.  Interleukin (IL)-15 and IL-7 Jointly Regulate Homeostatic Proliferation of Memory Phenotype CD8+ Cells but Are Not Required for Memory Phenotype CD4+ Cells , 2002, The Journal of experimental medicine.

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

[51]  R. Kurlander,et al.  Analysis of the time course of IFN-gamma mRNA and protein production during primary murine listeriosis. The immune phase of bacterial elimination is not temporally linked to IFN production in vivo. , 1991, Journal of immunology.

[52]  Yanan Zhu,et al.  Molecular mechanisms of activated T cell death in vivo. , 2002, Current opinion in immunology.

[53]  S. Akira,et al.  Toll-like receptors. , 2003, Annual review of immunology.

[54]  P. Morrissey,et al.  Impaired survival and proliferation in IL-7 receptor-deficient peripheral T cells. , 1996, Journal of immunology.

[55]  S. Jameson,et al.  Multiple Choices , 2002, The Journal of experimental medicine.

[56]  Wolfgang Weninger,et al.  Migratory Properties of Naive, Effector, and Memory Cd8+ T Cells , 2001, The Journal of experimental medicine.