Activated cytotoxic T lymphocytes (CTL) directly recognize and kill cells expressing foreign antigen. The activation of T lymphocytes into functional CTL occurs through triggering in response to the recognition of antigen as well as lymphokine signals. Recent work by this lab indicates that multiple lymphokines IL-2. IFN-delta and a lymphokine functionally referred to as cytotoxic differentiation factor (CDF) are involved in the generation of CTL. Recent progress in the ability to isolate genes encoding specific proteins has resulted in the isolation-of several different lymphokines. The BSF-1/IL-4, BSF-2/IL-6 and BCGFII/IL-5 lymphokines were initially isolated because of their effects on B lymphocytes but are now thought to play a major role in the development of mature T lymphocytes. We will attempt to define how these different lymphokines function together to bring about the differentiation and activation of CTL. Our long term goals are 1) to identify the lymphokines involved with the activation of CTL in vitro and 2) determine if administering the required lymphokines in vivo will enhance the generation of CTL to poorly recognized targets such as tumor cells. Lymphokines required for differentiation of CTL will be investigated by the use of recombinant lymphokines and the use of antibodies able to block the action of endogenous lymphokines. The lymphokine requirements will be defined for thymocytes as well as for mora mature T cells of the spleen and lymph nodes. We will also determine if the lymphokine requirements for triggering in response to alloantigen is the same as for self plus foreign antigen. Defining the lymphokine requirements for generation of CTL may lead to methods for generating in vivo responses against weak antigens such as virus infected tissue or malignant tissue as well as lead to techniques for inhibiting unwanted immune responses such as autoimmune reactions against self or reactions against transplanted tissue.
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