Immunologic memory is recognized as an antigen specific responses, occurring more rapidly, of higher magnitude, and over a longer duration than occurred following the first immunization. Although recognized for many years, the cellular and molecular events characterizing this memory response have to be fully understood. Our previous work revealed that CD4+T cells capable of exhibiting """"""""long-term memory"""""""" helper function are qualitatively different from naive T cells with regard to cell surface receptor expression, capacity to produce cytokines and survival mechanisms. In this application, we seek to identify key elements that define memory helper T cells.
In Aim 1, we propose to study the significance of the Thy-1 dependent 6C10 determinant, expressed at the highest levels by memory helper T cells. In the initiation of memory B-T interaction, Thy-1 may act as an adhesion molecule to enhance cellular interactions and also serve to amplify TCR dependent T cell activation. We will investigate whether retention of 6C10 expression, as a particular glycoform of Thy-1 (or as a Thy-1 associated molecule), is essential for function of memory helper T cells.
In Aim 2, we will investigate the importance of IL-2 production by memory helper T cells. Our recent data suggest that low IL-2 production by memory helper T cells may be sufficient to expand the memory T cell pool and thereby avoid cell depletion due to differentiation into short lived effector cells. We will determine whether low level IL-2 secretion is a critical aspect of memory helper T cells. Finally, in Aim 3, we will investigate how the memory T cell pool is maintained, focusing on the significance of IL-2 and up-regulated Bcl-xl expression. These studies will reveal the sequential molecular and cellular events occurring in the memory antibody response with the eventual aim of determining how such events can be manipulated, whether to enhance immunization or to ameliorate allergy and autoimmunity.
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