A mechanism of retinoid potentiation of murine T-cell responses: early upregulation of interleukin-2 receptors.
The capacity of retinoids to amplify the proliferative response of BALB/c lymphocytes to concanavalin A (Con A)2 in the presence of exogenous interleukin-2 (IL-2) and the induction of IL-2 receptors (IL-2R) on L3T4+ and Lyt-2+ T-cells was evaluated. Preincubation with Con A for 8 h in the presence of retinoids resulted in a greater than two-fold increase in spleen cell proliferative response to Con A plus rIL-2 over the following 72 h relative to the response of cells preincubated with Con A alone. Peak potentiation of IL-2 responses occurred over a pharmacologic range of retinoic acid (RA) concentration (10(-10)-10(-8) M) in the presence of 20 U/ml rIL-2. This potentiation of the response to IL-2 was likewise observed after 8 h prestimulation with Con A with splenic T-cells enriched by passage over nylon wool. Preincubation of the spleen cells with Con A plus RA without the subsequent addition of IL-2 resulted in a proliferative response that was potentiated nearly to the level of the response produced by subsequent addition of IL-2 to Con A-activated cells. Preincubation of the cells with Con A in the presence of RA produced a true synergy with IL-2; the resulting increase in response was greater than the sum of the increases produced by RA or IL-2 alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, Birmingham Veterans Administration Medical Center, AL.
X L
XL
Jiang
M P
MP
Everson
E W
EW
Lamon
D000818:Animals; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D012176:Retinoids / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D012176:Retinoids; D014212:Tretinoin