Inhibition of T and B lymphocyte proliferation by rapamycin.
The immunosuppressive macrolide rapamycin shows marked structural similarity to FK-506, and like FK-506 inhibits the activation of cultured T and B lymphocytes at concentrations as low as 10(-10) M. However, rapamycin blocks T-lymphocyte proliferation at a much later stage than FK-506. It also inhibits human, porcine and murine T- and B-lymphocyte activation by all pathways tested, including pathways which are insensitive to FK-506, such as interleukin-2 (IL-2)-mediated proliferation of IL-2-dependent T-cell lines, activation of human peripheral blood T lymphocytes by phorbol ester and anti-CD28 and activation of murine B lymphocytes by bacterial lipopolysaccharide. Thus these two macrolides that bind competitively to the same major intracellular receptor protein inhibit T- and B-lymphocyte activation by quite distinct mechanisms.
Kay
J E
JE
School of Biological Sciences, University of Sussex, Brighton, U.K.
Kromwel
L
L
Doe
S E
SE
Denyer
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology; D004347:Drug Interactions / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008934:Mitogens / Q000276:immunology; D011090:Polyenes / Q000494:pharmacology*; D020123:Sirolimus; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D008934:Mitogens; D011090:Polyenes; D020123:Sirolimus; D016559:Tacrolimus