UBC Theses and Dissertations
P815 tumor-specific T suppressor cell and suppressor factor Maier, Tom
The work reported here involves studies of suppressor T cells (T[sub=s]C) and their suppressor factor (SF) which specifically suppress the in vitro generation of cells cytotoxic for a syngeneic tumor, P815, in DBA/2 mice. This work can be divided into three sections: a) the immunogenetic properties and requirements of this T[sub=s]C and SF, b) the Lyt phenotype of the T[sub=s]C as well as that of the cells involved in the cytotoxic response to the syngeneic tumor, c) the properties of syngeneic and allogeneic antisera raised to the P815 specific SF. a) P815-antigen specific T[sub=s]C and suppressive extracts obtained from the thymuses of DBA/2 mice bearing small syngeneic P815 tumors, were compared for their immunogenetic properties and requirements. It was shown that pretreatment of T[sub=s]C populations with anti-la[sub=d] antiserum plus rabbit complement removed the suppressive activity. Similarly, absorption of the SF with anti-la[sup=d] antiserum removed the suppressive properties of the material. It was found that the T[sub=s]C and SF were capable of specifically suppressing the anti-P815 response of B6D2F₁ radiation chimeras possessing lymphoid cells of the H-2[sup=b] or H-2[sup=t2] haplotype equally as well as they could suppress the response of H-2[sup=d] bearing cells. This indicates that the T[sub=s]C and SF are not H-2 restricted with respect to K or D markers on responder cells in this system. b) T[sub=s]C were also identified in the spleens of DBA/2 mice injected intraperitoneally with membrane extracts of the P815 tumor. The Lyt phenotypes of various effector cells was determined. DBA/2 allogeneic killer cells were identified as Lyt-1⁺2⁺, whereas the syngeneic effector cells were found to be predominantly Lyt-1⁺2⁺. The suppressor cell population lost its ability to suppress the in vitro cytotoxic anti-P815 response after treatment with anti-Lyt-1 serum plus complement but not after treatment with anti-Lyt-2 serum, indicating that an Lyt-1⁺2⁻ cell is essential in this suppression. c) P815 tumor-specific SF was partially purified by passage of suppressive spleen extracts through an immunoadsorbent containing P815 membrane components. Antisera raised in syngeneic DBA/2 and allogeneic, C57BL/6, mice were tested. It was found that these antisera, but not their controls were capable of absorbing out the SF. The antisera were also capable, in the presence of complement, of eliminating T[sub=s]C from suppressive spleen cell populations. However, the antisera were not capable of eliminating syngeneic tumor specific in vitro generated killer cells, indicating that the receptor molecules on suppressor and effector cells in this system are distinct from each other. Only the antisera "raised in syngeneic DBA/2 mice had any observable effect on P815 tumor growth in vivo.