With a knowledge that immunogenic tumors evoke the generation of an antitumor immune response that is down-regulated by CD4+ suppressor T cells after the tumors reach a certain size, attempts will be made to further characterize suppressor T cells. The specificity of suppression will be tested by reciprocal passive transfer experiments designed to ensure that the suppression being tested does not decay because of the absence of an adequate quantity of tumor antigen in recipient mice. The time course of production of suppressor T cells, their life-span after passive transfer, and their ability to expand in number in vivo in response to exogenous IL-2 will be investigated. Suppression will also be studied in vitro to determine the conditions for growing suppressor T cells with the aim of cloning them for functional analysis. The immune response that is down-regulated by suppressors will be studied in terms of the production and distribution of effector T cells and their entry into the tumor. The cellular events associated with tumor regression will be studied to determine whether T cells can destroy a tumor by themselves, or whether, instead, they require the participation of other host cells. This will require the use of highly enriched effector/helper T cells from immunized donor mice, and tumor-bearing recipient mice that have been-rendered deficient in their capacity to contribute monocytes, neutrophils and NK cells to the regression process. In vitro expanded TIL and freshly harvested tumor-specific T cells will be compared in terms of their ability to destroy tumor deposits in the lung and to extravasate and destroy truly extravascular tumors.
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