Purpose- Both HIV and Mycobacterium tuberculosis infection have emerged as a challenging clinical problem worldwide . Moreover, there is a suggestion that HIV infected individuals who become infected with M. tuberculosis have an accelerated course of HIV- infection leading to a fatal outcome. Finally, the recent outbreak of patients with multi-drug resistant tuberculosis (MDRTB) in both HIV positive and negative individuals has been a cause of great public concern. Thus, the purpose of this work is to use an in vitro model to study cytokine regulation from PBMCs obtained from patients infected with HIV or multi-drug resistant tuberculosis. Our intent is to define whether there is a deficiency in cytokine production that could be important in their susceptibility to infection and determine whether the immune defect can be compensated by cytokines or costimulatory ligands. In addition we will use costimulatory ligand agonists to study their effects on cytokine and B-chemokine production of macrophages and dendritic cells. In addition, we will determine whether agonists such as soluble CD40L are able to alter the function of these antigen presenting cells, thus altering the function of CD4 and CD8+ T cells as well. Scope and Work- Blood will be obtained from normals or individuals infected with HIV and MDRTB and separated into PBMCs and purified population of T cells. Cells will then be stimulated in vitro with a variety of specific HIV and TB antigens as well as polyclonal mitogens. Proliferative, cytokine (IFNg, IL-4, IL-12, IL-10 TNFa) and B-chemokine responses will be determined. In addition, cytokines, cytokine antagonists or costimulatory ligands will be added to cultures to determine whether the immune responses can be qualitatively and quantitatively altered.
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