An analysis of T lymphocyte subsets in tumour-transplanted mice on the basis of Lyt antigenic markers and functions

Abstract

Small lymphocyte subsets were characterized radioautographically on the basis of several surface markers, viz. surface Ig (S-Ig), Thy-1 and Lyt (Ly-1, Ly-2 and 3) antigens in host lymphoid organs (thymus, spleen and blood) as well as at the tumour site at various stages of subcutaneous growth of two different syngeneic tumours—MPC-11 plasmacytoma and WEHI-164 fibrosarcoma in BALB/c mice. In both tumour-host combinations there was a rise in the levels of null (S-Ig^-, Thy-1^-) small lymphocytes as well as the Ly-23⁺ subset of T small lymphocytes at all the sites examined. The absolute number of these two subsets also increased excepting the case of null cell rise in the thymus which was relative. The functional potentials of Lyt subsets were explored by employing in vitro and in vivo assays. While no appreciable levels of anti-tumour cytotoxic T cells (T_c) were detectable by a ⁵¹Cr release assay in the host spleen or the tumour-draining lymph nodes at any stage of growth of MPC-11 tumour, such T_c was generated in vitro by a co-cultivation of unprimed spleen cells with irradiated MPC-11 cells. These T_c were Thy-1⁺ and Ly-12⁺, as noted from antibody+C′ mediated abrogation of cytotoxicity. These results suggested that the generation of anti-tumour T_c in vivo was suppressed in tumour-bearing hosts. The possibility of a cell-mediated suppression was tested by an adoptive transfer of thymocytes or splenocytes from tumour-bearing mice into naive or pre-immunized recipients which then received fresh tumour transplants. This procedure caused a specific enhancement of tumour growth in three tumour-host combinations: MPC-11 or WEHI-164 tumour in BALB/c mice and W-1 fibrosarcoma in CBA mice. The suppressor lineage lymphocytes appearing in vivo were found to be Thy-1⁺ and Ly-1^-, 2⁺, as noted from antibody +C′ mediated abrogation of their tumour-growth promoting ability. They appeared earlier (7 days) in the thymus and later (>2 weeks) in the spleen and then persisted during the tumour lifetime. The parallel kinetics of the increase in the overall level of Ly-23⁺ cells and the appearance of Ly-2(3)⁺ suppressor lineage T cells in tumour-bearing hosts may indicate that studies of T-cell surface markers may be useful in predicting changes in the functional lymphocyte subsets.