Human thymic epithelial cells directly induce activation of autologous immature thymocytes.
To study the role that epithelial cells of the thymic microenvironment play in promoting activation of immature CD7+, CD2+, CD4-, CD8- (double-negative) human thymocytes, we have isolated thymocyte subsets from normal postnatal thymus and have cocultured autologous double-negative thymocytes with pure populations of thymic epithelial (TE) cells. We report that TE cells directly activate double-negative thymocytes to proliferate and that TE cells enhance the ability of double-negative thymocytes to proliferate in response to stimulation with exogenous interleukin 2. Activated double-negative thymocytes that proliferated in vitro in the presence of TE cells and interleukin 2 remained double-negative after 23 days in culture. Moreover, TE-cell culture supernatants in the absence of intact TE cells contain interleukin 1, interleukin 3, and granulocyte/macrophage-colony-stimulating factor activity for human bone marrow cells and can activate double-negative thymocytes to proliferate. Antibodies against interleukin 1 and against granulocyte/macrophage-colony-stimulating factor inhibited TE-cell-induced thymocyte activation. These data indicate that one role of TE cells in vivo may be to activate double-negative thymocytes to proliferate.
D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D004847:Epithelial Cells; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000096:biosynthesis; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000166:cytology*; D013936:Thymidine / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology*
D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D013936:Thymidine