Immunological enhancement of a murine tumor allograft by passive alloantibody IgG and F(ab')2.

The F(ab')2 fraction of an anti-tumor IgG alloantiserum induced passive enhancement of tumor allografts in inbred mice about as well as did intact IgG; i.e. apparently the Fc fragment is not required for suppressing cellular immunity. Passive F(ab')2, however, was somewhat less efficient than intact IgG or whole alloantiserum in depressing the allohemagglutinin response. The latter finding is in accord with previous observations on the relative inefficiency of F(ab')2 in feedback inhibition of the humoral response of mice to a heteroantigen.

Induction of peritoneal ascites fluid by Freund's adjuvant: Genetic and hormonal influences.

Strain differences among inbred mice is demonstrated for the relative amounts of peritoneal ascites fluid induced by the injection of Freund's adjuvant and antigen. Females tend to produce more fluid than males; the lower level in males is attributable to the action of male hormone. Both genetic and epigenetic factors are determinants in the response levels; genetic factors differentiate the inbred strains of mice, epigenetic factors underlie the variations within a strain and the difference between sexes.

Antibody-mediated suppression of grafted lymphoma. III. Evaluation of the role of thymic function, non-thymus-derived lymphocytes, macrophages, platelets, and polymorphonuclear leukocytes in syngeneic and allogeneic hosts.

Syngeneic or allogeneic mice pretreated with sublethal whole-body irradiation were rendered incapable of suppressing the growth of grafted tumor cells sensitized with alloantibody. The growth of sensitized tumor cells was suppressed when they were mixed with donor effector cells from mice syngeneic or allogeneic to the recipients and then were inoculated in irradiated recipients. Three donor-host combinations were used to study the suppression of the murine lymphoma 6C3HED indigenous to C3H mice. These were C3H donor cells in C3H recipients, C57BL/6 donor cells in C3H recipients, or C57BL/6 donor cells in C57BL/6 recipients. In all three combinations, macrophages obtained from an inflammatory exudate, exudate lymphocytes not bearing theta antigen, and platelets were, in descending order of effectiveness, consistently active in restoring antibody-mediated suppression of tumor growth in irradiated hosts. Prior irradiation of the transferred lymphocytes somewhat diminished their effectiveness. Freeze-thawed or heat-killed macrophages (but not freeze-thawed platelets or lymphocytes) were effective in restoration. Peripheral blood mononuclear leukocytes and splenic lymphoid cells were not active in the recipients syngeneic to the donor cells but were acitve in recipients allogeneic to the donor cells. Polymorphonuclear leukocytes isolated from peripheral blood or an inflammatory exudate were not active. Intact thymic function seems unimportant since antibody-mediated suppression took place as effectively in thymectomized mice as in normal controls.

Characteristics of histocompatibility barriers in congenic strains of mice. III. Passive enhancement of skin allografts in X-irradiated hosts.

Passive immunological enhancement of skin allografts was investigated in three donor-host combinations of congenic mice disparate at non-H-2 loci. Serum against the graft donor was derived from mice that had received donor strain lymphoid cells as neonates, and thereby were rendered specifically tolerant of a skin allograft. We refer to this serum as "allograft-tolerant" serum. Each strain combination was chosen to provide only two non-H-2 histoincompatibilities present in the donor and absent in the host. The differences are categorized as immunogenetically strong, moderate, or weak, on the basis of skin allograft survival times. With passively administered allograft-tolerant serum significantly prolonged graft survivals were noted for the weakest combination only. Combined treatment with sublethal X-irradiation and allograft-tolerant serum signigicantly prolonged graft survivals were noted for the weakest combination only. Combined treatment with sublethal X-irradiation and allograft-tolerant serum significantly prolonged graft survival in both the moderate and weak combinations, with the largest effect present in the weakest disparity. A hyperimmune alloantiserum (produced in adults) directed against the graft donor prolonged allograft survival in the strongest disparity when given in combination with irradiation. In this combination, graft survival time was increased in hosts exposed to X-ray alone, but joint treatment with X-ray and the alloantiserum gave the largest increment. In contrast, combined treatment with the serum and an antithymocyte alloantiserum did not affect graft survival times. Treatment with both radiation and antithymocyte serum did not prolong graft survival beyond that in mice given only X-radiation. Immunological enhancement with central inhibition is assumed as the mechanism underlying prolonged graft survival, and it is suggested that a population of thymus-derived "killer" cells, sensitive to X-irradiation, is required for normal graft rejection.

Antibody-mediated suppression of grafted lymphoma cells. II. Participation of macrophages.

Specific alloantibody admixed with a grafted murine lymphoma is suppressive of the graft in mice of the inbred strain native to the tumor. Suppressive capacity of the host is obviated in mice given 500 R whole body irradiation before tumor inoculation but is restored when normal peritoneal macrophages are admixed with the tumor-antibody inoculum. Other normal cell types admixed with the tumor-antibody inoculum are not effective in restoring suppressive capacity.