Naïve and Memory CD4+ T Cell Survival Controlled by Clonal Abundance

Immunity to a plethora of microbes depends on a diverse repertoire of naïve lymphocytes and the production of long-lived memory cells. We present evidence here that low clonal abundance in a polyclonal repertoire favors the survival and activation of naïve CD4+ T cells as well as the survival of their memory cell progeny. The inverse relation between clonal frequency and survival suggests that intraclonal competition could help maintain an optimally diverse repertoire of T cells and an optimal environment for the generation of long-lived memory cells.

[1]  A. Rudensky,et al.  Survival and Homeostatic Proliferation of Naive Peripheral CD4+ T Cells in the Absence of Self Peptide:MHC Complexes1 , 2000, The Journal of Immunology.

[2]  D. Loh,et al.  Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. , 1994, Immunity.

[3]  Benedict Seddon,et al.  Interleukin 7 and T cell receptor signals regulate homeostasis of CD4 memory cells , 2003, Nature Immunology.

[4]  M. Meier-Schellersheim,et al.  Spontaneous proliferation, a response of naive CD4 T cells determined by the diversity of the memory cell repertoire. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[5]  S. Varga,et al.  Independent Regulation of Lymphocytic Choriomeningitis Virus-Specific T Cell Memory Pools: Relative Stability of CD4 Memory Under Conditions of CD8 Memory T Cell Loss1 , 2001, The Journal of Immunology.

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

[7]  M. Jenkins,et al.  Tracking salmonella-specific CD4 T cells in vivo reveals a local mucosal response to a disseminated infection. , 2002, Immunity.

[8]  C Benoist,et al.  How much TCR does a T cell need? , 2001, Immunity.

[9]  Emmanuel Beaudoing,et al.  Size Estimate of the αβ TCR Repertoire of Naive Mouse Splenocytes1 , 2000, The Journal of Immunology.

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

[11]  A. Heimberger,et al.  Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo. , 1990, Science.

[12]  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.

[13]  Leo Lefrançois,et al.  Initial T cell frequency dictates memory CD8+ T cell lineage commitment , 2005, Nature Immunology.

[14]  A. Khoruts,et al.  Competition for self ligands restrains homeostatic proliferation of naive CD4 T cells , 2003, Proceedings of the National Academy of Sciences of the United States of America.

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

[16]  C. Surh,et al.  A Role for TCR Affinity in Regulating Naive T Cell Homeostasis 1 , 2004, The Journal of Immunology.

[17]  I. Messaoudi,et al.  The many important facets of T-cell repertoire diversity , 2004, Nature Reviews Immunology.

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

[19]  A. Khoruts,et al.  Visualizing the generation of memory CD4 T cells in the whole body , 2001, Nature.

[20]  A. Troy,et al.  Cutting Edge: Homeostatic Proliferation of Peripheral T Lymphocytes Is Regulated by Clonal Competition1 , 2003, The Journal of Immunology.

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