REGULATION OF IL-2 RECEPTOR BY THE CD4 LIGAND IL-16

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IL-16 was identified, characterized and cloned in the laboratory of Dr. Parada's co-sponsors, Drs. Center and Cruikshank. One of the functions of IL-16 is a selective activation for CD4+ T cells. Other major functions include chemotactic activity for all CD4+ leukocytes, a competence growth factor for CD4+ T cells, inhibition of the mixed lymphocyte reaction and TcR activation, and inhibition of HIV-1 replication. All of IL-16`s functions require Cdr which it utilizes as part of its membrane recognition unit. Suggesting that CD4 has functions other than as the recognized intercellular adhesion molecule complementary to MHC II molecules during antigen presentation. These other functions of CD4, namely as a chemotactic and growth factor receptor are mediated by interaction with its natural lymphokine ligand, IL-16. Dr. Parada's studies with IL-16 demonstrate that signaling through CD4 can take place independent of the TcR and CD3 and result in cell migration and cell cycle progression to an IL-2R, IL-2R, G1 competence point. Recent studies in their laboratory have shown that long term treatment (over four weeks) with a combination of IL-16 and IL-2 leads to a dramatic synergistic increase in CD4 cells expressing IL-2R. This proposal will explore the relationship between IL-16 induced CD4- dependent activation of transcription factors associated with IL-2R and IL-2R expression. Experiments described below will be performed to identify IL-16- responsive elements within the IL-2R and gene expression. This will allow Dr. Parada to learn and apply molecular biology techniques while allowing her to establish herself as an IL-16 expert with an independent project that is a logical extension of her scientific goals.