Putative role for interleukin-7 in the maintenance of the recirculating naive CD4+ T-cell pool.
The capacity of the immune system to respond efficiently to new antigens depends upon a continuous source of naive CD4+ T cells. Such cells exit from the thymus and join the recirculated T-cell pool. Factors present at the sites of naive CD4+ T-cell circulation must be responsible for their survival, since upon removal from their host, naive CD4+ T cells die. However, such factors remain unknown. The presence of the cytokine interleukin-7 (IL-7) in secondary lymphoid organs and the continuous expression of its receptor on naive CD4+ T cells prompted us to examine the possibility that IL-7 might be a survival factor for naive CD4+ T cells. Using naive CD4+ T cells isolated from cord blood we show that IL-7, but not IL-2, can maintain naive CD4+ T-cell viability in vitro for at least 15 days. In addition, we find that IL-7 can induce modest proliferation of naive CD4+ T cells without affecting either their cell surface phenotype or their ability to respond to antigenic stimulation. We also find that after anti-CD3 stimulation, naive CD4+ T cells lose that ability to respond to IL-7. However, if cells are primed with IL-7 prior to antigenic stimulation, their proliferative responses are enhanced. Together, these data suggest a novel and important role for IL-7 in the maintenance and maturation of naive CD4+ T cells, ensuring that they can respond maximally when they first meet antigen in secondary lymphoid tissue.
Webb
L M
LM
Kennedy Institute of Rheumatology, Hammersmith, London, UK.
Foxwell
B M
BM
Feldmann
M
M
D017951:Antigen Presentation; D017252:CD3 Complex / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology; D015851:Interleukin-7 / Q000494:pharmacology / Q000502:physiology*; D008221:Lymphoid Tissue / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
D017252:CD3 Complex; D007376:Interleukin-2; D015851:Interleukin-7