Cocaine augments proliferation of human peripheral blood T-lymphocytes activated with anti-CD3 antibody.
Previously we observed that cocaine can suppress the phytohemagglutinin-induced proliferation of cultured, purified human T-lymphocytes. However, because the receptor activation pathways stimulated by this mitogen are not fully understood, we decided in the present study to examine the effects of cocaine on T-lymphocyte cultures stimulated with the anti-CD3 antibody which is known to stimulate these cells through the T-cell receptor complex. The results show that cocaine augments T-lymphocyte proliferation to anti-CD3 stimulation at drug concentrations observed in the blood of cocaine abusers. This augmentation was dose dependent reaching a plateau at a concentration above 0.75 microM. The amount of interleukin-2 (IL-2), as measured by ELISA, in the supernatants of T-cell cultures and the level of cytosolic free-calcium (Ca2+) mobilization in the T-cells were also increased at approximately the same concentrations that increased proliferation. Cocaine treatment alone had no effects on proliferation, IL-2 production, or Ca2+ mobilization. These results suggest that cocaine augments proliferation of human T-lymphocytes when the cells are activated through the T-cell receptor complex by increasing cytosolic Ca2+ mobilization and subsequent IL-2 production.
Matsui
K
K
Department of Medical Microbiology and Immunology, University of South Florida, College of Medicine, Tampa 33612.
Friedman
H
H
Klein
T W
TW
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D017136:Ion Transport / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007376:Interleukin-2; D003042:Cocaine; D002118:Calcium