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Recombinant DNA-derived interferons-alpha and -beta modulate the alloactivated proliferative response of bulk and
We studied the effect of cloned human interferons-alpha and -beta (IFN-alpha and IFN-beta) upon human peripheral blood lymphocytes stimulated in primary mixed lymphocyte cultures (MLC). We herein demonstrate that three of these IFN preparations (IFN-alpha 76, -alpha 54, -beta ser), as well as naturally produced IFN-beta, can each affect MLC in opposing ways. When stimulator cells are limited, IFN-alpha and -beta are inhibitory. At higher stimulating cell concentrations, IFN augments the MLC response. This potentiation of the proliferative response is IFN dose-dependent and is not due to a shift in the kinetics of the proliferative response. When T cell clones were tested in the proliferative assay, IFN-alpha 76 was shown to have a direct antiproliferative effect. Both the potentiation and inhibition of primary bulk MLC responses could result from the direct antiproliferative effect of exogenous IFN. The potentiation of some proliferative responses by IFN in bulk culture may reflect a preferential inhibition of immunoregulatory (suppressor) cells. Moreover, these dichotomous effects of IFN on primary alloactivated cultures suggest that caution should be used when extrapolating from these in vitro results to potential in vivo effects.
We studied the effect of cloned human interferons-alpha and -beta (IFN-alpha and IFN-beta) upon human peripheral blood lymphocytes stimulated in primary mixed lymphocyte cultures (MLC). We herein demonstrate that three of these IFN preparations (IFN-alpha 76, -alpha 54, -beta ser), as well as naturally produced IFN-beta, can each affect MLC in opposing ways. When stimulator cells are limited, IFN-alpha and -beta are inhibitory. At higher stimulating cell concentrations, IFN augments the MLC response. This potentiation of the proliferative response is IFN dose-dependent and is not due to a shift in the kinetics of the proliferative response. When T cell clones were tested in the proliferative assay, IFN-alpha 76 was shown to have a direct antiproliferative effect. Both the potentiation and inhibition of primary bulk MLC responses could result from the direct antiproliferative effect of exogenous IFN. The potentiation of some proliferative responses by IFN in bulk culture may reflect a preferential inhibition of immunoregulatory (suppressor) cells. Moreover, these dichotomous effects of IFN on primary alloactivated cultures suggest that caution should be used when extrapolating from these in vitro results to potential in vivo effects.