In vitro induction of CD8 expression on thymic pre-T cells. I. Transforming growth factor-beta and tumor necrosis factor-alpha induce CD8 expression on CD8- thymic subsets including the CD25+CD3-CD4-CD8- pre-T cell subset.
We previously reported that IL-7 maintains the viability and differentiation potential of CD25 (IL-2R p55) positive CD3-CD4-CD8- thymic pre-T cells in vitro. This culture system is suitable for studying signals that regulate differentiation of T cell precursors in the thymus. In this study, we screened cytokines for their capacity to induce CD4 or CD8 in murine thymic pre-T cells cultured with IL-7. Of 15 cytokines tested, only transforming growth factor (TGF-beta) and TNF-alpha induced CD8 (Lyt-2), while no cytokine was able to induce CD4 on CD25+CD3-CD4-CD8- thymocytes. The combination of TGF-beta and TNF-alpha was synergistic, and the majority of cells recovered after 2 to 3 days in culture expressed CD8 (but not CD3 or CD4). A similar effect of TGF-beta and TNF-alpha was observed using day-15 fetal thymocytes, CD3+CD4-CD8- or CD3+CD4+CD8- adult thymocytes, although the combination of these cytokines resulted in an additive rather than a synergistic effect in these subsets. In contrast, neither TGF-beta nor TNF-alpha induced CD8 expression on splenic CD4+CD8- T cells. These observations suggest a role for these cytokines in the induction of CD8 expression in CD8- thymocyte subsets including CD3-CD4-CD8- thymic pre-T cells.
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D005434:Flow Cytometry; D066298:In Vitro Techniques; D015851:Interleukin-7 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016827:CD8 Antigens; D015851:Interleukin-7; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha