High concentrations of interleukin-2 selectively suppress T-cell dependent humoral immune responses

The recent therapeutic application of immunoregulatory cytokines, most notably the T-cell growth factor, interleukin-2 (IL-2), marks the advent of a new class of pharmacologic agents. In the present studies the effects of exogenous IL-2 on in vitro humoral immune responses in spleen cells isolated from female B6C3F1 mice were investigated. In vitro direct addition of low concentrations of rmIL-2 (25 U/ml) to naive spleen cells induced a moderate enhancement of the T-cell dependent antibody forming cell (AFC) response to sRBC. Similarly, low concentrations of rmIL-2 (10-50 U/ml) enhanced T-cell independent AFC responses to DNP-Ficoll and LPS. Interestingly, high concentrations of rmIL-2 (100 or 250 U/ml) selectively suppressed the T-cell dependent AFC response but not T-cell independent AFC responses to either DNP-Ficoll or LPS. Neither immunoenhancing (25 U/ml) nor immunosuppressive (200 U/ml) concentrations of rmIL-2 altered the kinetics of the sRBC response. Temporal addition studies indicated that high concentrations of rmIL-2 (200 U/ml) were only inhibitory when added to the cultures during the first 24 h following antigen sensitization. Conversely, a significant enhancement of the response was observed when 200 U/ml rmIL-2 was added 48 h following antigen sensitization. These results are in agreement with previous reports that the presence of high concentrations of IL-2 render T-cells unresponsive to subsequent antigen stimulation but that the high concentrations of IL-2 enhance immune responses when added at 48 h following antigen sensitization.