HLA‐DR Antigens Render Interleukin‐2‐Producer T Lymphocytes Sensitive to Interleukin‐1

Monoclonal anti‐HLA‐DR antibodies inhibited the production of interleukin‐2 (IL‐2) when added from the initiation of autologous (AMLR) and allogeneic (MLR) mixed lymphocyte reactions, but not 60 h later. The inhibitory activity of the anti‐DR sera became apparent 8 h after initiation of the cultures and was maintained throughout the culture period. Interleukin‐1 (IL‐1) added to cultures carried out in the absence of the anti‐DR antibodies significantly enhanced the production of IL‐2, whereas addition of IL‐1 to anti‐DR‐treated AMLR and MLR cultures did not restore or increase the synthesis of IL‐2. However, when the anti‐DR antibodies were added to IL‐1‐supplemented AMLR and MLR cultures 60 h or more after initiation of the reactions, the antiserum no longer inhibited the capacity of IL‐1 to promote the synthesis of IL‐2 or the production of IL‐2. Finally, resting T cells were unresponsive to IL‐1 and did not produce IL‐2. It thus seemed that the anti‐DR antibodies inhibited production of IL‐2 in AMLR and MLR by rendering the IL‐2 producer T cells unresponsive to IL‐1. Cyclosporin‐A, a drug that abrogates activation of T cells by blocking their receptors for HLA‐DR antigens, also rendered IL‐2‐producer T cells unresponsive to IL‐1 and abrogated the production of IL‐2 in AMLR and MLR. Since resting T cells do not respond to IL‐1 or produce IL‐2, it is concluded that HLA‐DR antigens of the stimulator cells participate in the production of IL‐2 in AMLR and MLR by enabling the IL‐2 producer T lymphocytes to respond to IL‐1. Interleukin‐1 promotes the production of IL‐2 by IL‐1‐sensitive T cells. Once the IL‐2‐producer T cells become sensitive to IL‐1, there is no further requirement for HLA‐DR antigens.