Synergistic role of type I interferons in the induction of protective cytotoxic T lymphocytes.

Differentiation of cytolytic T cells can be supported by type I and type II interferons (IFN). To characterize the role of type I interferons further we tested the role of recombinant IFN-alpha and IFN-beta on the induction of a weak immune response, against a low immunogenic tumor, which has been shown to be increased by IFN. Both type I interferons IFN-alpha and IFN-beta were able to support the differentiation of cytolytic T lymphocytes (CTL). In case of IFN-alpha no correlation with the antiviral activity could be seen by comparison of IFN-alpha1 and IFN-alpha4. The maximal in vitro effects were achieved with very low concentrations in the range of 1-100 IU/ml. IFN-alpha showed the strongest effects, if added in the early phase of the mixed leukocyte culture, whereas IFN-beta was most effective when given at the last day the culture. In combination, both IFNs gave additional/synergistic effects, whereby addition of IFN-alpha at day 0 and IFN-beta at day 4 led to maximal specific CTL responses. In vivo augmentation of the anti-tumor immune response by both types of IFNs supported the in vitro findings and also the synergistic effect of both types of IFNs could be demonstrated. Therefore we propose that IFN-alpha is relevant in the induction of CTL responses, i.e., the conversion of precursor T cell into mature cells and growth promotion whereby IFN-beta might trigger the lytic machinery of the cells and promote differentiation. This synergistic efficacy is also operative in tumor rejection.