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This paper describes a model of successful immunotherapy of advanced lymphoma based on the selective elimination of cycling tumour-induced suppressor T cells. It shows that a single injection of the anti-mitotic drug, vinblasting (Vb), results in complete regression of a large L5178Y lymphoma and its metastases, but not if it is growing in an immunocompetent host. Vb-induced, immunologically mediated tumour regression was dependent on the anti-tumour function of CD8+ T cells, because regression was prevented by depleting the host of this subset of T cells 24 hr after Vb was given. Regression was also prevented by infusing the host with Vb-sensitive, CD4+ T cells from a turnout-bearing donor. These and other results are in keeping with the interpretation that Vbinduced regression of the L5178Y lymphoma depends on the ability of the drug to eliminate CD4+ suppressor T ceils that are replicating, and to spare non-replicating CD8+ effector cells, it is suggested that at an advanced stage of growth of the L5178Y lymphoma the host possesses an acquired population of antigen-primed CD8+ effector T cells that are unable to become activated in response to abundant tumour antigen because of the dominant influence of CD4+ suppressor cells. Activation of these CD8+ T cells was indicated by the finding that they were rapidly converted from being cyclophosphamide (Cy) resistant to being highly Cy sensitive within 48 hr of giving Vb. [ABSTRACT FROM AUTHOR]

It has been shown that progressive growth of the P815 mastocytoma in its semisyngeneic B6D2 host results, between days 6 and 9 of tumour growth, in the generation of Ly 1-2+ T cells which are capable, on passive transfer, of causing the regression of an established tumour in γ-irradiated recipients, and of T cells which are capable of lysing P815 tumour cells in vitro. After 9 days of tumour growth, these effector T cells are progressively lost; this is associated with the progressive acquisition of Ly 1+2- suppressor T cells which are capable of inhibiting the expression of passively transferred immunity against an established tumour in T-cell deficient recipients. The results are consistent with the hypothesis that this P815 mastocyroma grows progressively, in spite of its immunogenicity, because it evokes the generation of suppressor T cells before enough effector T cells are generated to reject it. [ABSTRACT FROM AUTHOR]