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Interleukin 2 Requirement for the in Vitro Generation of Antitumor Cytotoxicity by Thymocytes from Melphalan-cured MOPC-315 Tumor Bearers¹

Department of Microbiology and Immunology, University of Illinois at Chicago Health Science Center, Chicago, Illinois 60612

We have previously shown that enhanced antitumor cytotoxicity is generated when thymocytes from melphalan (L-phenylalanine mustard; L-PAM)-treated MOPC-315 tumor bearers, but not thymocytes from normal mice, are added to the immunization culture of syngeneic normal spleen cells and MOPC-315 tumor cells (Bartik et al., Cancer Res., 47: 4848–4855, 1987). Here we show that normal spleen cells produce, upon stimulation with MOPC-315 tumor cells, helper-like factors which are sufficient for thymocytes from L-PAM-treated MOPC-315 tumor bearers, but not for thymocytes from normal mice, to develop antitumor cytotoxicity in response to stimulation with MOPC-315 tumor cells. Since one of the helper-like factors produced by in vitro-immunized spleen cells is interleukin 2 (IL-2), we assessed the exogenous IL-2 requirements for the development of anti-MOPC-315 cytotoxicity in thymocytes from L-PAM-treated MOPC-315 tumor bearers, relative to thymocytes from normal mice. Thymocytes from L-PAM-treated MOPC-315 tumor bearers were found to require a 10-fold lower concentration of recombinant IL-2 (rIL-2) than thymocytes from normal mice in order to develop antitumor cytotoxicity in response to stimulation with MOPC-315 tumor cells. The concentration of rIL-2 required for the development of anti-MOPC-315 cytotoxicity by thymocytes from L-PAM-treated MOPC-315 tumor bearers was also 10-fold lower than the concentration of rIL-2 required by thymocytes from untreated MOPC-315 tumor bearers or thymocytes from L-PAM-treated normal mice. In addition, at any concentration of rIL-2 employed, thymocytes from L-PAM-treated MOPC-315 tumor bearers developed a higher level of anti-MOPC-315 cytotoxicity than did thymocytes from normal mice, L-PAM-treated normal mice, or untreated MOPC-315 tumor bearers. The enhanced antitumor cytotoxicity exhibited by thymocytes from L-PAM-treated MOPC-315 tumor bearers, following in vitro stimulation with MOPC-315 tumor cells plus rIL-2, was evident not only against MOPC-315 tumor cells but also against other syngeneic plasmacytomas but not an allogeneic thymoma. In addition, thymocytes from L-PAM-treated MOPC-315 tumor bearers required less rIL-2 than thymocytes from normal mice to develop antitumor cytotoxicity in response to stimulation with MOPC-315-associated antigens but not in response to stimulation with an allogeneic antigenically unrelated thymoma (EL4). Thus, L-PAM treatment of MOPC-315 tumor bearers, but not of normal mice, leads to a substantial reduction in the concentration of exogenous IL-2 required by their thymocytes in order to develop an antitumor cytotoxic response against plasmacytoma-associated antigens.

¹ Supported by Research Grant CA-35761 from the National Cancer Institute and Research Grant IM-435 from the American Cancer Society.

² To whom requests for reprints should be addressed, at The University of Illinois, Microbiology and Immunology MC 790, 835 South Wolcott Avenue, Chicago, IL 60612.

³ In partial fulfillment of the requirements for the Doctor of Philosophy degree.

Received 3/ 7/88. Revised 7/19/88. Revised 11/ 4/88. Accepted 11/15/88.