IL-10, A NOVEL GROWTH COFACTOR FOR MATURE AND IMMATURE T-CELLS

We identified a new cytokine, B cell-derived T cell growth factor (B-TCGF), that is produced by a murine B cell lymphoma and induces proliferation of mature and immature thymocytes in the presence of IL-2 and IL-4. Both adult and day 15 fetal thymocytes (CD4-8-, CD4+8-, CD4-8+) proliferate strongly in the presence of IL-2, IL-4, and B-TCGF. B-TCGF alone does not stimulate thymocyte proliferation. B-TCGF appears to be identical to a novel cytokine whose cDNA was recently isolated at our institution, cytokine synthesis-inhibitory factor (CSIF; IL-10). rIL-10 has B-TCGF activity, and mAb specific for IL-10 inhibit the B-TCGF activity present in CH12 supernatants. Further studies have shown that day 15 fetal thymocytes cultured in the presence of IL-10, IL-2, and IL-4 remain CD4- and CD8- but exhibit increased CD3 expression. Adult CD4- CD8- thymocytes cultured under the same conditions proliferate whether they are CD3+ or CD3-. The CD3- population becomes enriched in CD3+ cells after 4 days of culture. IL-10 is secreted by day 15 fetal thymocytes, adult thymocytes, and adult splenocytes when stimulated via their TCR. IL-10 is strongly homologous to the EBV gene BCRFI, and BCRFI has CSIF activity. In contrast to IL-10, BCRFI does not exhibit detectable thymocyte-stimulating activity, suggesting the existence of at least two functional epitopes on the IL-10 molecule.