Interferons alpha/beta inhibit IL-7-induced proliferation of CD4- CD8- CD3- CD44+ CD25+ thymocytes, but do not inhibit that of CD4- CD8- CD3- CD44- CD25- thymocytes.
Type 1 interferons (IFN-alpha/beta) have recently been shown to inhibit interleukin-7 (IL-7)-induced growth and survival of early B-lineage cells. The CD3- CD4- CD8- (triple negative; TN) thymocytes from normal mice strongly proliferated upon stimulation with IL-7 in suspension, culture. Such an IL-7-induced proliferation was suppressed by the addition of IFN-alpha/beta, but a fraction of the TN thymocytes still showed proliferation. The IL-7-induced growth of TN thymocytes from acid mice, which lack the CD44- CD25- subpopulation, was completely inhibited by the addition of IFN-alpha/beta. The IL-7 induced proliferation of CD4- CD8- thymocytes from T-cell receptor (TCR) transgenic mice, the majority of which are CD3+ CD44- CD25-, was resistant to IFN-alpha/beta-mediated suppression. In fetal thymus organ cultures (FTOC), the addition of IL-7 greatly increased the population of CD4- CD8- CD44+ CD25+ thymocytes and IFN-alpha/beta inhibited this IL-7-driven expansion. In contrast, the addition of IL-7 markedly decreased the percentages of CD4- CD8- CD3- CD44- CD25- cells, and IFN-alpha/beta reversed the effect and increased the subpopulations of CD44- CD25+ and CD44- CD25-. Finally, IFN-beta mRNA was found to be expressed in the thymus. The data suggest that type I interferons inhibit IL-7-driven proliferation of TN thymocytes, but do not block the normal differentiation process.
Su
D M
DM
Department of Molecular Immunology, Kyushu University, Fukuoka, Japan.
Wang
J
J
Lin
Q
Q
Cooper
M D
MD
Watanabe
T
T
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D005260:Female; D007370:Interferon Type I / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D015703:Antigens, CD; D007370:Interferon Type I; D015851:Interleukin-7