Recombinant interleukin-7 induces proliferation of naive macaque CD4+ and CD8+ T cells in vivo.
Interleukin-7 (IL-7) regulates T-cell homeostasis, and its availability is augmented in lymphopenic hosts. Naive CD8+ T cells transferred to lymphopenic mice acquire a memory-like phenotype, raising the possibility that IL-7 is the biological mediator of this effect. Here, we provide direct evidence that IL-7 induces the acquisition of memory-cell markers not only in CD8+ T cells but also in CD4+ T-cell subsets in immune-competent Indian rhesus macaques. The increase of these memory-like populations was dependent on the dose of the cytokine, and these cells were found in the blood as well as secondary lymphoid organs. Memory-like CD4+ and CD8+ T cells acquired the ability to secrete tumor necrosis factor alpha and, to a lesser extent, gamma interferon following stimulation with a cognate antigen. The phenotypic change observed in naive T cells was promptly reversed after discontinuation of IL-7. Importantly, IL-7 induced cycling of both CD4+ and CD8+ central memory and effector memory T cells, demonstrating its contribution to the maintenance of the entire T-cell pool. Thus, IL-7 may be of benefit in the treatment of iatrogenic or virus-induced T-cell depletion.
Moniuszko
Marcin
M
Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bldg. 41, Rm. D804, Bethesda, MD 20892-5065, USA.
Fry
Terry
T
Tsai
Wen-Po
WP
Morre
Michel
M
Assouline
Brigitte
B
Cortez
Pierre
P
Lewis
Mark G
MG
Cairns
Scott
S
Mackall
Crystal
C
Franchini
Genoveffa
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D007156:Immunologic Memory; D015851:Interleukin-7 / Q000494:pharmacology*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008231:Lymphopenia / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008253:Macaca mulatta; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015851:Interleukin-7; D019394:Ki-67 Antigen; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha