One of the characteristic cellular immune responses associated with the regression of Moloney leukemia/sarcoma virus-induced tumors is a T cell proliferative response against the major viral envelope glycoprotein, gp70. The results described here demonstrated that associated with this proliferative response is the production of a lymphokine, Interleukin 3 (IL-3). The production of IL-3 was immunologically specific and showed the same specificity as that observed in blastogenic responses. IL-3 production was dependent upon an antigen-specific Thy-1.2+, Lyt-1+, 2- lymphocyte subpopulation but did not require the presence of an Ia+ or an adherent accessory cell. The results also suggested that IL-3 may constitute one of the blastogenic factors previously shown to be involved in the proliferative response to gp70. In particular, purified IL-3 was found to induce proliferation of both normal and immune nylon wool purified splenic lymphocytes. The phenotype of the responding lymphocyte subpopulation was Thy-1.2-, Lyt-1-, 2-, Ig-, and Ia-. Maximal IL-3 production occurred approximately 48 hr after the addition of antigen and its production was significantly blocked by mitomycin C. These characteristics were unlike those for the general production of blastogenic factor activity suggesting that IL-3 is responsible for only a minor component of the proliferative response.

The characteristics of the blastogenic response of splenic lymphocytes from MoLV/MSV immune mice was examined. Splenic lymphocytes from immune mice proliferate in vitro in response to the major virion envelope glycoprotein, gp70. Associated with this response is production of blastogenic factors that induce the proliferation of nylon wool-purified lymphocytes from either normal or immune mice. The phenotype of antigen-specific lymphocytes essential for the production of blastogenic factors was found to be Thy 1.2+, Lyt 1+, 2-. The induction of proliferation by blastogenic factors does not require the presence of antigen. Using splenic lymphocytes from either normal or immune mice, blastogenic factors predominantly induce the proliferation of a Thy 1.2-, Lyt 1-, 2- lymphocyte. As a consequence of responding to blastogenic factors, in vitro, approximately 50% of this lymphocyte population becomes Thy 1.2+, Lyt 1+ over a period of 3 days. The frequencies of lymphocytes producing and responding to blastogenic factors were found to show characteristic changes during the course of tumor growth and regression.