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 scid 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 1 interferons inhibit IL-7-driven proliferation of TN thymocytes, but do not block the normal differentiation process.