Effect of cyclosporin A on the anti-CD3 antibody- and concanavalin A-induced activation and membrane potential of human T lymphocytes.
The immunosuppressive effect of cyclosporin A (CsA) was studied on the anti-CD3 antibody (anti-CD3)- and concanavalin A (Con A)-induced activation of human T lymphocytes. A similar suppressive effect was observed in the Con A- and anti-CD3-induced proliferation as measured by the amount of [3H]thymidine incorporated on the third day of culture. When the cells were washed 30 min after activation with anti-CD3, the response was diminished and the CsA sensitivity was increased. In contrast, addition of interleukin-2 (IL-2) resulted in a significantly increased response and a decreased sensitivity. In cultures activated with anti-CD3, CsA treatment resulted in suppression of proliferation after 3 days and an enhancement after 5 days. This latter phenomenon was not seen in cultures treated with Con A. Removal of macrophages (MPH) abolished the proliferative response to anti-CD3. The addition of 10% MPH restored the response, while pretreatment of MPH with CsA diminished this ability. There were differences in the activation kinetics elicited by these two agents as reflected by the changes in membrane potential and the rate of IL-2 receptor (Tac) expression. The changes in the membrane potential (in the absence of CsA) seemed to be parallel with Tac expression and thymidine incorporation. CsA caused a hyperpolarization of the cell membrane. Both Con A and anti-CD3 brought about a strong depolarization which was blocked by the presence of CsA.
Gergely
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Division of Research and Testing, Food and Drug Administration, Washington, DC 20204.
Aszalos
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D000906:Antibodies / Q000008:administration & dosage; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003208:Concanavalin A / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008564:Membrane Potentials / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D013936:Thymidine / Q000378:metabolism
D000906:Antibodies; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003524:Cyclosporins; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D003208:Concanavalin A; D013936:Thymidine