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Hybrid Resistance to BALB/c Plasmacytomas: F₁ Hybrid Anti-MPC-11 Immunological Responses Correlated with Resistance to Tumor Challenge¹

Department of Pathology and Kaplan Cancer Center, New York University Medical Center, New York, New York 10016

BALB/cJ x C57BL/10Sn F₁ (hereafter called B10F₁) hybrids resist challenge with the BALB/c plasmacytoma, MPC-11, by a radiation-sensitive, silica-insensitive mechanism, whereas BALB/cJ x BALB.B F₁) hybrids are as susceptible to MPC-11 as are homozygous BALB/c mice themselves. To investigate the mechanism of resistance, we have compared anti-MPC-11 immune responses by these F₁ hybrids both before and at various times after tumor challenge. Resistance is not determined by natural killer cell reactivity inasmuch as neither hybrid harbors splenic natural killer cells with lytic activity directed against MPC-11. Nor is it determined by antibody-dependent cell-mediated cytotoxicity since neither hybrid produces an appropriate anti-MPC-11 antibody. Spleen cells and lymph node cells from both hybrids are capable of generating high levels of anti-MPC-11 cytotoxic T-lymphocyte activity in both primary and secondary mixed-lymphocyte tumor cell cultures. Such cytotoxic T-lymphocytes protect susceptible hybrids from tumor growth in Winn assays. The susceptible but not the resistant hybrids lose the ability to generate high levels of cytotoxic T-lymphocytes activity in spleen mixed lymphocyte tumor cell cultures by 28 days, and in lymph node mixed-lymphocyte tumor cell cultures by 14 days postchallenge. The reduction in spleen cell reactivity is due to suppression mainly by adherent cells and can be abrogated by pretreatment of the susceptible hybrids with a low dose of Cytoxan 2 days before challenge. This pretreatment does not, however, protect the mice. They develop tumor at the same rate and die at the same time as do controls. Both the late appearance of suppression and the lack of effect on survival of its ablation suggest it to be a concomitant of tumor growth rather than its cause. Resistance to tumor growth in this model system may reflect an enhanced ability of the resistant hybrid to deliver effector cells to the site of tumor implantation.

¹ Supported by ACS Grant IM 213.

² Present address: Jefferson Medical College, Box 556, Philadelphia, PA 19106.

³ Present address: Institut Armand Frappier, U. Quebec, 531 boul. des Prairies, Laval, Quebec, H7N4Z3 Canada.

⁴ To whom requests for reprints should be addressed, at Department of Pathology, New York University Medical Center, 550 First Avenue, New York, NY 10016.

Received 12/18/84. Revised 10/ 1/85. Accepted 10/ 4/85.