Antiviral CD4+ memory T cells are IL-15 dependent.
Survival and intermittent proliferation of memory CD4(+) and CD8(+) T cells appear to be controlled by different homeostatic mechanisms. In particular, contact with interleukin (IL)-15 has a decisive influence on memory CD8(+) cells, but not memory CD4(+) cells. Past studies of memory CD4(+) cells have relied heavily on the use of naturally occurring memory phenotype (MP) cells as a surrogate for antigen (Ag)-specific memory cells. However, we show here that MP CD4(+) cells contain a prominent subset of rapidly proliferating major histocompatibility complex (MHC) II-dependent cells. In contrast, Ag-specific memory CD4 cells have a slow turnover rate and are MHC II independent. In irradiated hosts, these latter cells ignore IL-15 and expand in response to the elevated levels of IL-7 in the lymphopenic hosts. In contrast, in normal nonlymphopenic hosts where IL-7 levels are low, memory CD4 cells are heavily dependent on IL-15. Significantly, memory CD4(+) responsiveness to endogenous IL-15 reflects marked competition from other cells, especially CD8(+) and natural killer cells, and increases considerably after removal of these cells. Therefore, under normal physiological conditions, homeostasis of CD8(+) and CD4(+) memory cells is quite similar and involves IL-15 and IL-7.
Purton
Jared F
JF
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Tan
Joyce T
JT
Rubinstein
Mark P
MP
Kim
David M
DM
Sprent
Jonathan
J
Surh
Charles D
CD
D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D006706:Homeostasis; D007156:Immunologic Memory / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology* / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D010641:Phenotype
D000941:Antigens; D019409:Interleukin-15; D015851:Interleukin-7