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in Vivo Cooperation of Murine Lymphocytes Sharing One Haplotype of the Transplantation Genes: A Requirement for Tolerance of the Nonshared Haplotype¹

Matko Marui² and Eugene H. Perkins

From the University of Tennessee-Oak Ridge Graduate School of Biomedical Sciences, and Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830

Abstract

The ability of mouse thymus-dependent (T) and bone marrow-derived (B) lymphocytes to cooperate in the (humoral) rejection of the rat Yoshida ascites sarcoma (YAS) was investigated. Mice of two hybrid constitutions that had one parent of the same strain and the other of a different strain were used. T and B cells thus shared one haplotype of the transplantation genes, but the other haplotype was different so that allogeneic recognition could take place in both directions. To investigate the influence of allogeneic recognition on T-B cell cooperation, mice were also made mutually tolerant by establishing long-term radiation chimeras. Erythrocytes and spleen cells of the chimera were shown by serologic analysis to be donor-type. When the chimera was to serve as tumor host and B cell source, it was thymectomized before irradiation and reconstitution with Thy 1.2 antisera and complement-treated bone marrow (TIR). The evidence of tolerance was markedly reduced anti-host-type reactivity in short-term in vivo [³H]thymidine uptake studies. Successful cooperation, manifested by YAS rejection in TIR mice given splenic T cells, was seen a) whenever the transferred T cells and the cells of the TIR recipient were syngeneic, and b) when the T cells were nonsyngeneic with the cells in TIR recipients but were obtained from chimeric donors and injected into chimeric recipients. Chimerism of only T cell donors or TIR recipients was not sufficient for YAS rejection to be induced. The data suggest that the allogeneic recognition on either T or B lymphocytes may thwart otherwise successful cell cooperation.

Footnotes

¹ This work was supported by the Division of Biomedical and Environmental Research, United States Department of Energy, under Contract W-7405-eng-26 with the Union Carbide Corporation.

² Postdoctoral Investigator supported by Subcontract No. 3322 from the Biology Division of Oak Ridge National Laboratory to the University of Tennessee, and by the Fulbright-Hays Program. Present address: Department of Physiology, University of Zagreb Faculty of Medicine, 41000 Zagreb, Salata 3, Yugoslavia.