Immunization with antigen and interleukin 2 in vivo overcomes Ir gene low responsiveness

We studied the effect of purified interleukin 2 (IL-2), made by recombinant DNA techniques, on the serum antibody response to myoglobin in high- and low-responder mice. Previous studies (6, 7) have shown that this response is controlled by H-2-linked Ir genes. The IL-2 was emulsified with the antigen in complete Freund's adjuvant to provide a sustained high local concentration. In low-responder B10.BR mice, a single dose (optimum 50,000 U) resulted in a consistent 10-50-fold increase in specific serum antibody throughout the time course of the response, from 10 d to 46 d after immunization. In contrast, no effect of IL-2 was seen in congenic high-responder B10.D2 mice. With IL-2, the low-responder mice achieved specific antibody levels comparable to those of high responders. Vehicle alone had no effect, and IL-2 alone, without antigen, did not induce myoglobin-specific antibody. No effect of IL-2 was seen in athymic nude mice of high-responder H-2 haplotype. The effect of IL-2 may be on a small number of responding T cells in the low responder mice, but it is possible that IL-2 also acts directly on B cells in a response that remains T-dependent, and therefore is not observed in athymic mice. We suggest that IL-2 may enhance suboptimal T cell help in the low responder, whereas help is not limiting in the high responder. This approach may enable the study of antibody responses in low responders otherwise too weak to analyze, and may be useful in producing antibodies to poorly immunogenic antigens. Potential clinical uses include immunization with weak antigens in normal patients, or with any antigen in certain immunodeficient patients.