Tumor necrosis factor-alpha and P40 induce day 15 murine fetal thymocyte proliferation in combination with IL-2.
Cytokines are known to play a key role in the development of several hemopoietic lineages including lymphocytes. Two cytokines: IL-4 (in the presence of PMA) and IL-7 have been shown to induce immature fetal thymocyte proliferation. It has also been suggested that IL-2 plays an important role in fetal T cell development. In this report, we investigated the effects of several cytokines (known to be growth factors for T-lineage cells) on fetal thymocyte proliferation. Our results indicate that: 1) TNF-alpha and a newly described cytokine, P40, enhance fetal thymocyte proliferation stimulated by IL-2 (but not IL-4 or IL-7). 2) The enhancement induced by P40 is not mediated by TNF-alpha because blocking antibodies against this cytokine failed to inhibit this response. 3) IL-4 inhibits fetal thymocyte proliferation in response to TNF-alpha + IL-2 or to IL-7 but not to P40 + IL-2. Finally, 4) the proliferating cells to all cytokine combinations used were Thy-1+. These observations suggest that these cytokine combinations induce independent pathways of T cell proliferation in the developing thymus.
Suda
T
T
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.
Murray
R
R
Fischer
M
M
Yokota
T
T
Zlotnik
A
A
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001685:Biological Factors / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines; D004357:Drug Synergism; D006023:Glycoproteins / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D016906:Interleukin-9; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology*; D051379:Mice; D018800:Thy-1 Antigens; D013950:Thymus Gland / Q000196:embryology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000954:Antigens, Surface; D001685:Biological Factors; D016207:Cytokines; D006023:Glycoproteins; D006133:Growth Substances; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D016906:Interleukin-9; D018800:Thy-1 Antigens; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4