A strong cell-mediated immune response against Friend, Moloney, Rauscher virus-induced (FMR) cell surface antigens has been demonstrated previously in mice which reject oncornavirus-induced tumors. In order to identify an eventual suppressor mechanism in animals with progressively growing tumors, experiments were initiated in C57BL/6 mice bearing either a murine sarcoma virus (MSV) tumor or Moloney virus-induced lymphoma (MBL2). Progressive tumor growth was induced (a) in viremic animals first infected with Moloney murine leukemia virus (M.Mu LV), then inoculated as adult with MSV; (b) in nonviremic animals injected with MBL2 lymphoma cells. In the absence of tumor cells, viremia induces specific tolerance for which there is no evidence for suppressor cells. In tumor-bearing mice, specific suppressor T cells are detected which are able to inhibit the generation of anti-FMR cytolytic T lymphocytes in vitro and enhance the tumor growth in vivo. In addition to the specific suppressor T cells, a nonspecific suppressive activity mediated by metastatic T lymphoma cells is demonstrated in the spleens of lymphoma-bearing animals. The respective role of the virus and tumor cells in the induction of tolerance to M.MuLV-induced antigens, and their relationship to other components of the specific cell-mediated immune response is discussed.

The role of the Fc receptor (FcR) of thymus-derived I y m phocytes Presence of FcR on suppressor cells and direct involvement in suppression*Alloantigen-activated T cells (ATC) were prepared by injecting C3H/He thymocytes into host-irradiated BALB/c mice. ATC were taken from the spleen of the recipients at day 5 and tested for their activity o n "in vitro" primary antibody production t o sheep red blood cells (SRBC) induced in splenic C3H/He lymphocytes. ATC added 24 h after antigen were found t o be suppressive. Separation of ATC by velocity sedimentation, according t o cell size showed that suppressor cells were found in each population, medium and large lymphocytes, however, being more active. Separation of ATC, according t o the presence of Fc receptor (FcR) at their membrane was achieved by velocity sedimentation after rosetting with IgG-sensitized SRBC (EA). Suppressor cells were then found in FcR+ and not in FcR-fractions, the degree of suppression being parallel t o the ratio of FcR+ cells. At both extremes, pure populations of FcR+ cells were highly suppressive, while populations of ATC, completely devoid of FcR' cells, were inactive. Since FcR is a very labile molecule a t the T cell surface and shed within 3 h at 37 "C, but not at 4 "C, ATC were pre-incubated at each temperature and added 24 h after antigen t o the spleen cell cultures. In these cases, ATC having released their FcR, were much less suppressive than control ATC, and in previous work we have shown that the suppressive activity was found in the cell supernatant associated with an FcR-like molecule (immunoglobulin-binding factor). The data therefore allow the conclusion that FcR may be a marker of nonantigen-specific suppressor T cells and seems t o be involved itself in the suppression phenomenon.

The role of the Fc receptor (FcR) of thymus-derived I y m p hocy t es I. Presence of FcR on cytotoxic lymphocytes and absence of direct role in cytotoxicity*Cytotoxic T lymphocytes (CTL) were prepared by injecting C3H/He (H-2k) thymocytes into host-irradiated BALB/b (H-2b) mice. Specific cytolysis was measured o n MBL2 lymphoma cells from C57BL/6 (H-2b) mice. Alloantigenactivated T cells (ATC) were taken from the spleens of the recipients at day 5 and separated according to size and/or t o the presence of membrane F c r e c e p tors (FcR) b y the use of velocity sedimentation techniques. The data showed that CTL were found in populations of lymphocytes heterogeneous in cell size and were always present in the FcR-positive population. Depletion of FcRpositive ATC, after rosetting with IgC-sensitized sheep erythrocytes led t o an abolishment of cytolytic activity while enrichment in FcR-positive ATC led to a parallel increase of cytolytic activity. Taking advantage of the rapid release of FcR at 37 OC by ATC, we investigated the direct involvement of the FcR molecule in cytolysis. We found that ATC which had released their FcR after pre-incubation for 2 h a t 37 OC exerted the same level of cytotoxicity as control ATC incubated at 4 OC. The data lead us, therefore, t o conclude that FcR may be a marker of differentiation of cytotoxic T cells found in the spleen, but does not itself play a role in the cytolytic reaction.