Inhibition of T cell development in thymic organ culture: implications for the mechanism of action of cyclosporin A.
We have examined the effects of the immunosuppressive drug cyclosporin A (CsA) on the phenotypic maturation of T cells in thymic organ cultures begun at day 16 of gestation. CsA specifically inhibited the generation of cells expressing high levels of alpha/beta TcR/CD3 complexes and a mature phenotype defined by CD4 and CD8 surface markers. Adding interleukin (IL) 1 beta, IL 2 or IL 4 failed to reverse the effects of CsA, and major histocompatibility complex class II expression in the thymic medulla was preserved. Possible mechanisms of CsA-mediated inhibition of T cell development are discussed.
Siegel
R M
RM
Department of Pathology, University of Pennsylvania Medical School, Philadelphia.
Yui
K
K
Tenenholz
D E
DE
Kubo
R
R
Greene
M I
MI
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007378:Interleukins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003524:Cyclosporins; D000949:Histocompatibility Antigens Class II; D007378:Interleukins; D011948:Receptors, Antigen, T-Cell