Involvement of avidity for major histocompatibility complex in homeostasis of naive and memory T cells.
The requirements for survival and self-renewal of peripheral T cells and the nature of mechanisms controlling the size of the naive and memory pool are not completely understood. Here, we examine the involvement of the major histocompatibility complex (MHC) in survival and homeostatic expansion of naive and memory T cells. We show that the homeostatic behavior of naive T cell receptor (TCR)-transgenic T cells can be deduced by the expression levels of TCR and CD5, a negative regulator of TCR signaling. Both these factors determine the strength of TCR stimulation by MHC-derived signals. We further show that, similarly to naive T cells, MHC-derived signals influence the homeostatic expansion capacity of memory T cells under lymphopenic conditions. In contrast to naive T cells, however, memory T cells can reach a homeostatic equilibrium, in which survival/self-renewal of each clone is dissociated from their avidity for MHC-derived signals.
Kassiotis
George
G
Division of Molecular Immunology, The National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
Zamoyska
Rose
R
Stockinger
Brigitta
B
D019264:Adoptive Transfer; D000818:Animals; D000915:Antibody Affinity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018956:CD5 Antigens / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D006649:Histocompatibility Antigens / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis; D007156:Immunologic Memory; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D018956:CD5 Antigens; D006649:Histocompatibility Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020395:Receptors, Interleukin-7