T lymphocytes and their CD4 subset are direct targets for the inhibitory effect of calcitriol.
We studied the direct effects of the hormone calcitriol on the activation and proliferation of pure T lymphocytes and their subsets. Calcitriol inhibited the proliferation of T lymphocytes stimulated in the absence of monocytes with phytohemagglutinin (PHA) and either a monocytic culture supernatant or a combination of monocyte-derived interleukin 1 and interleukin 6. This inhibition was not influenced by the concentration of the stimulating agents. The minimal effective concentration of calcitriol was 10(-10) M. In contrast, the interleukin 2 (10 U/ml)-driven growth of PHA-stimulated T lymphocytes was not significantly altered by calcitriol at 10(-8) M. The hormone had also no influence on the T lymphocyte proliferation induced by a combination of PHA and the anti-CD28 monoclonal antibody 9.3. Pure T lymphocytes, after incubation for 5 days with PHA and monocytic factors, expressed a high level of transferrin receptors. This phenomenon was strongly suppressed on both CD4 and CD8 subsets when 10(-8) M calcitriol had been present during the culture. Moreover, the proliferation of pure CD4 cells was directly inhibited by calcitriol in similar conditions as for unseparated T lymphocytes. We conclude that T lymphocytes and their CD4 subset are direct targets for the inhibitory effect of calcitriol.
Vanham
G
G
LEGENDO, Onderwijs en Navorsing, Gasthuisberg, Leuven, Belgium.
Ceuppens
J L
JL
Bouillon
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018106:CD28 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007165:Immunosuppression Therapy; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000276:immunology; D015846:Monokines / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D015846:Monokines; D010835:Phytohemagglutinins; D011990:Receptors, Transferrin; D002117:Calcitriol