Regulatory role of T lymphocytes and NK cells in tumor allograft development

Abstract

In the present study, the respective roles of T cells and their subpopulations as well as of NK (natural killer) cells in antitumor immune responses were followed using the SaI (H-2a) allograft model. The development of this tumor in B10 (H-2b) mice was evaluated after pretreatment of the recipients with xenogeneic antithymocyte serum (ATS). Anti-Thy 1.2, anti-Lyt 2.2 and anti-L3T4 monoclonal antibodies were used in order to determine T lymphocyte phenotypes and to assess the frequency of TC/S and TH subpopulations at various periods of tumor development. Rabbit polyclonal anti-asialo GM1 antiserum was used for the identification of NK cells. In a previous work it was suggested that the first week following transplantation, the cells predominantly involved in the growth regulation of SaI belong to the TS subclass. Our results based on the use of anti-Lyt 2.2 monoclonal antibodies have further supported this finding. The application of anti-Thy 1.2 on the 3rd and 5th day has hampered a secondary tumor growth while anti-Lyt 2.2 was effective when given on day 5. The depletion of Lyt. 2.2+ cells on day 3 resulted in the inhibition of both primary and secondary tumor development. On the other hand, when anti-Thy 1.2 was applied on day 7 after transplantation, the primary and secondary tumor growth was strikingly enhanced. It appears that Thy 1.2+ lymphocytes display at this period effector functions and contribute, in conjunction with macrophages, to subsequent tumor regression. The depletion of L3T4 cells on days 3 and 5 after tumor inoculation has resulted in primary tumor growth enhancement. This suggests that cells of the L3T4+ phenotype display at this time helper functions contributing to CTL proliferation and maturation. A further indication, supporting the possible suppressor effect of L3T4+ cells, counts from the finding that anti-L3T4 treatment results in an inhibition of secondary tumor growth. The anti-asialo GM1 treatment has not enhanced, at least significantly, primary tumor development but has partially or totally inhibited the growth of secondary tumors. It appears that cells of the GM1+ (NK cells) phenotype do not participate in any substantial way in the early phases of SaI tumor development in ATS treated allogeneic recipients.