The numerous reports (1) showing that suppressor T cells are generated in response to growth of immunogenic tumors serve to provide an explanation for the paradoxical growth of these tumors in their immunocompetent syngeneic hosts. A recent publication (2) from this laboratory revealed, for example, that progressive growth of a transplantable murine tumor, the Meth A fibrosarcoma, results in the generation in the host of a T cell-mediated state of immunosuppression that prevents the regression of this tumor by passively transferred, tumor-sensitized T cells from immune donors. The presence of suppressor T cells in the tumor-bearing host was revealed in two ways: first, by showing that in order to demonstrate adoptive T cell-mediated regression of established tumors, it was necessary to use tumor-bearing recipients that had been made T cell deficient by thymectomy and gamma irradiation; second, by demonstrating that adoptive T cell-mediated regression of tumors in these T celldeficient recipients could be inhibited by prior infusion of splenic T cells from T cellintact, tumor-bearing donors. It was concluded that the failure of passively transferred, sensitized T cells to cause tumor regression in T cell-intact mice was caused by the presence in these mice of a tumor-induced state of T cell-mediated immunosuppression.The main purpose of this paper is to show that a strikingly similar mechanism of immunosuppression is generated in response to growth of the P815 mastocytoma. It will show, in addition, that passive transfer of sensitized T cells not only causes complete regression of the primary tumor but also causes the destruction of tumor metastases. Materials and MethodsMice. B6D2 (C57BL/6 × DBA/2), F1, CB6 (BALB/c × C57BL/6)F1, DBA/2, and BALB/c mice of either sex were used when they were between 8 and 12 wk of age. They were supplied by the Trudeau Institute Animal Breeding Facility.

Since the original description of the therapeutic action of Co~ynebacterium parvum in a syngeneic murine tumor system over a decade ago (1), many reports have appeared (2-4) describing the anti-tumor action of this agent against syngeneic and autochthonous tumors in animals, and against tumors in man. The efficacy of anti-tumor therapy with C. parvum varies greatly among different tumor-host systems and depends on such factors as tumor immunogenicity (3, 5), tumor size and location (2, 3, 6), the amount of C. parvum used (7,8), and its route of administration (2). Depending upon the route of administration, C. parvum may elicit different anti-tumor mechanisms (2). Intravenous administration appears to favor the generation of nonspecific effector mechanisms, which are expressed by activated macrophages or natural killer cells (2, 3, 9-11). Intralesional therapy with C. paroum, on the other hand, is thought to favor the generation of T cell-mediated anti-tumor immunity, as evidenced by the finding that the anti-tumor action depends on the presence of a functional T cell system (8, 12, 13). Moreover, it has been shown that animals that have regressed their tumors after intralesional therapy with C. parvum display specific resistance to the growth of a tumor challenge implant (7,14), and possess T cells that are capable of passively transferring anti-tumor resistance to normal recipients (12,14). On the other hand, C. parvum has also been shown to enhance the growth of tumors, presumably because of its capacity to induce the generation of suppressor mechanisms (15,16).The main purpose of this paper is to describe a model currently being used to analyze the potential and limitations of tumor immunotherapy with C. parvum. It will show that when P815 tumor cells are admixed with C. parvum and implanted subcutaneously, the tumor that emerges grows for 9 d and then regresses. It will also show that the mechanism responsible for this regression is capable of causing the regression of an untreated test tumor growing at a distant site, and that this therapeutic action is based on a T cell-mediated immune response to tumor-specific transplantation antigens. It will show, finally, that the immunotherapeutic action of the C. parvum-tumor cell admixture against a distant test tumor is limited to a test tumor below a certain critical size. The companion paper (17) will deal with the reasons for this therapeutic limitation.

Certain Staphylococcus aureus strains, when inoculated into the peritoneal cavity of mice, were clumped and surrounded by a thick layer of leukocytes. After being enclosed with a connective tissue capsule, the structures histologically resembled staphylococcal abscesses. Of four strains examined, all were destroyed within abscesses, although at different rates. Abscess homogenates possessed bactericidal activity toward staphylococci, and this activity was associated with the sedimentable fraction of the homogenates. Leukocytes did not appear to be responsible for the bactericidal activity. Appreciable quantities of alpha toxin accumulated in these abscesses even without multiplication of the organisms. This model infection offers opportunities for studying some aspects of staphylococcal host-parasite interactions occurring in localized lesions.

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