Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells

Immunological memory depends on the long-term maintenance of memory T cells. Although the factors that maintain CD8 T cell memory are well understood, those responsible for CD4 memory are not well defined. We have shown here that interleukin 7 (IL-7) was an important survival factor for CD4 memory T cells that together with T cell receptor (TCR) signals regulated homeostasis of the CD4 memory population in lymphopenic conditions and in the intact immune system. Thus, IL-7 contributes to the maintenance of all naive and memory T cell subsets, and therefore controls the overall size of the T cell pool.

[1]  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.

[2]  S. Jameson,et al.  Homeostatic expansion and phenotypic conversion of naïve T cells in response to self peptide/MHC ligands. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[3]  P. Marrack,et al.  RANTES production by memory phenotype T cells is controlled by a posttranscriptional, TCR-dependent process. , 2002, Immunity.

[4]  中嶋 裕史 The common cytokine receptor γ chain plays an essential role in regulating lymphoid homeostasis , 1999 .

[5]  J. Sprent T and B memory cells , 1994, Cell.

[6]  S. Burdach,et al.  Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine , 1995, The Journal of experimental medicine.

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

[8]  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.

[9]  B. Rocha,et al.  Population biology of lymphocytes: the flight for survival. , 2000, Annual review of immunology.

[10]  R. Zamoyska,et al.  TCR Signals Mediated by Src Family Kinases Are Essential for the Survival of Naive T Cells1 , 2002, The Journal of Immunology.

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

[12]  D. Kioussis,et al.  Inducible expression of a p56Lck transgene reveals a central role for Lck in the differentiation of CD4 SP thymocytes. , 2000, Immunity.

[13]  T. Brocker Survival of Mature CD4 T Lymphocytes Is Dependent on Major Histocompatibility Complex Class II–expressing Dendritic Cells , 1997, The Journal of experimental medicine.

[14]  J. Sprent,et al.  Turnover of Naive-and Memory-phenotype T Cells , 1994 .

[15]  K. Rajewsky,et al.  How αβ T cells deal with induced TCRα ablation , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  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.

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

[18]  C. Janeway,et al.  Designing and maintaining the mature TCR repertoire: the continuum of self-peptide:self-MHC complex recognition. , 1999, Immunity.

[19]  F. Lemonnier,et al.  Differential requirements for survival and proliferation of CD8 naïve or memory T cells. , 1997, Science.

[20]  C. Benoist,et al.  T lymphocytes need IL-7 but not IL-4 or IL-6 to survive in vivo. , 2001, International immunology.

[21]  A. Berns,et al.  Peripheral T Cell Survival Requires Continual Ligation of the T Cell Receptor to Major Histocompatibility Complex–Encoded Molecules , 1997, The Journal of experimental medicine.

[22]  W. Leonard,et al.  Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. , 1995, Immunity.

[23]  B. Stockinger,et al.  Impairment of immunological memory in the absence of MHC despite survival of memory T cells , 2002, Nature Immunology.

[24]  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.

[25]  Richard Murray,et al.  IL-7 is critical for homeostatic proliferation and survival of naïve T cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  C Benoist,et al.  Tetracycline-controllable selection of CD4(+) T cells: half-life and survival signals in the absence of major histocompatibility complex class II molecules. , 2000, The Journal of experimental medicine.

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

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

[29]  R. Zamoyska,et al.  TCR and IL-7 Receptor Signals Can Operate Independently or Synergize to Promote Lymphopenia-Induced Expansion of Naive T Cells1 , 2002, The Journal of Immunology.

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

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

[32]  L. Berg,et al.  Cutting Edge : Two Distinct Mechanisms Lead to Impaired T Cell Homeostasis in Janus Kinase 3and 3and 3and CTLA4Deficient CTLA4Deficient CTLA4Deficient 4Deficient 4Deficient Mice 1 , 2000 .

[33]  G. Legname,et al.  Long-term survival but impaired homeostatic proliferation of Naïve T cells in the absence of p56lck. , 2000, Science.

[34]  C. Benoist,et al.  Targeted complementation of MHC class II deficiency by intrathymic delivery of recombinant adenoviruses. , 1997, Immunity.

[35]  R. Germain,et al.  CD4+ T cell survival is not directly linked to self-MHC–induced TCR signaling , 2000, Nature Immunology.

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

[37]  A. Sharpe,et al.  Defects in B Lymphocyte Maturation and T Lymphocyte Activation in Mice Lacking Jak3 , 1995, Science.

[38]  O. Lantz,et al.  γ chain required for naïve CD4+ T cell survival but not for antigen proliferation , 2000, Nature Immunology.

[39]  S. Swain,et al.  Class II-independent generation of CD4 memory T cells from effectors. , 1999, Science.

[40]  M. Croft,et al.  Helper T‐Cell Subsets: Phenotype, Function and the Role of Lymphokines in Regulating their Development , 1991, Immunological reviews.

[41]  C. Ware,et al.  Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice , 1994, The Journal of experimental medicine.