| Clinical Immunology Section |
 |
Dennis Taub, Ph.D., Acting Chief
Investigator |
| Overview: The research interests of my laboratory are focused in several areas including: (1) the molecular and cellular mechanisms of age-related defects in lymphocyte activation, differentiation, and effector function; (2) the biological, biochemical and molecular characterization of chemokines and their receptors on various immune populations; (3) the effects of aging and cell differentiation on HIV infectivity and propagation within primate lymphocytes and monocytes; and (4) the clinical and pre-clinical development of immunologically-based protocols focusing on promoting T-cell responses in elderly patients. |
| The recruitment of lymphocytes into inflammatory sites requires several activation events including endothelial cell activation by inflammatory cytokines, the expression of adhesion molecules, cellular adhesion, diapedesis, and migration via established chemotactic gradients. Chemokines have been shown to induce adhesion, chemotaxis, activation, and degranulation of human and rodent leukocytes and lymphocytes both in vitro and in vivo. Our laboratory is currently examining a role for chemokines and various G protein receptor ligands in lymphocyte activation and effector functions. Furthermore, studies examining the differential protein and gene expression of various cytokines and chemokines post cellular activation via mitogens, hormones, and stress factors are also under investigation. We believe that a better understanding of the complexities of leukocyte extravasation and the mediators that induce cell trafficking and activation will greatly assist our ability to orchestrate, regulate, and control various pathological disease states associated with aging as well as our understanding of normal leukocyte trafficking. |
| Recent reports have shown that AIDS in the elderly has dramatically increased over the past 5 years suggesting that immune cells obtained from older subjects have an increased susceptibility to HIV viruses. As various HIV strains utilize cell surface CD4 molecules and chemokine receptors to enter and subsequently infect T lymphocytes and monocytes, our studies have focused on the biological and molecular mechanisms involved in HIV binding and entry into young and aged immune cells as well as the differential expression of and signaling through various chemokine receptors. We believe that active transcriptional signals through CD4 and/or chemokine receptor molecules are required for optimal HIV infectivity and propagation. The identification and examination of induced or suppressed genes and proteins will not only provide insight into HIV pathogenesis but may also elucidate the molecular mechanisms of inflammation and the various signaling defects observed in aged lymphocytes. |
