Immune Reactivity in the Moloney Strain of Murine Sarcoma Virus Oncogenesis: Requirement of Thymus-Derived Lymphocytes for In Vivo Protection 2

Abstract

To study the function of different lymphocyte populations in the Moloney strain of murine sarcoma virus (M-MuSV) tumorigenesis, we gave M-MuSV injections to CBA mice selectively deprived of thymus (T) lymphocytes by thymectomy, X-rradiation, and syngeneic bone marrow injection. Although no tumors appeared in the control group, 80% of the derived mice had tumors that grew progressively and ultimately killed them. In deprived mice, grafted with a syngeneic thymus (reconstituted mice) before or after an M-MuSV injection, tumors regressed or did not develop. Histologically, the lymph nodes and spleens of reconstituted mice, compared to those of deprived animals, showed repopulation of the thymus-dependent areas and prominent follicles in the cortex. Moreover, tumor tissue of reconstituted mice was extensively infiltrated by lymphocytes. To evaluate the number of lymphoid cells needed to prevent or regress M-MuSV tumors, we injected varying amounts of lymphoid cells into deprived mice. Even low lymphocyte numbers (10(6) cells) were sufficient to exert, in some cases, protection against M-MuSV tumorigenesis. This effect was not abolished by subsequent splenectomy or antilymphocyte serum treatment. Finally, deprived mice, given repeated injections of antiserum (hyperimmune) against M-MuSV, had tumors which appeared only after a prolonged latency. From these results, it is concluded that T-cell population integrity is important in affording total host protection against the M-MuSV tumors.

Immunopathology

“…Results with antilymphocyte (ALS) or anti thymocyte (ATS) serum closely parellel those obtained by thymectomy. ALS/ATS enhances the incidence of adenovirus tumors in mice , polyoma tumors in mice ( Vandeputte, 1968;Allison and Law, 1968;AI-Falluji et al, 1969), MSV (Hook et ai., 1969;Zisblatt and Lilly, 1972;Collavo et al, 1976) and RSV (Banks et al, 1979) tumors in mice, and RSV tumors in baboons (Berman, unpublished observations). In the MSV system, an increased incidence of tumor development and progression was noted (Hook et al, 1969;Zisblatt and Lilly, 1972;Collavo et al, 1974).…”

“…Similar results were not obtained in the MSV-mouse system. However, normal lymphoid cells could reverse the tumorenhancing effect of thymectomy or irradiation in MSV-inoculated mice (Collavo et al, 1976).…”

“…It has been reported that X-irradiation increased tumor incidence and decreased the percent of tumor regressions in the MSV system (Fefer et al, 1967b;Gorczynski, 1974a;Collavo et al, 1976). Thymectomy at the time of virus inoculation or shortly thereafter significantly increased the incidence of adenovirus tumors in hamsters (Yohn et al, 1965;Samaille et al, 1967;Gasser and Loeffler, 1967;Van Hoosier et al, 1968;Larson et al, 1971) and mice ; polyoma virus tumors in hamsters (Larson et al, 1971), rats (Vandeputte et al, 1963), and mice (Malmgren et al, 1964;Mori et al, 1964;Gaugas et al, 1973);…”

“…SV40 tumors in rats (Allison and Taylor, 1967); and MSV sarcomas in mice (East and Harvey, 1968;Collavo et al, 1976). In addition, this treatment also produced tumors in some models where simple viral inoculation failed to produce lesions.…”

Growth pattern of tumours in mice induced by murine Moloney sarcoma-virus and sarcoma-virus-transformed cells

“…Re-quence of a sequence of immunological sults of these studies led to the assumption events during tumour development. In that the particularly strong immuno-immunoincompetent tumour-bearers there is no regression (Fefer et al, 1967;Collavo et al, 1976;Stutman, 1975; Davis, 1975); tumours grow progressively and lead to the death of their hosts.…”