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AbstractAn in vitromononuclear cell system to model the microenvironment of coinfection with HIV-1 and Mycobacterium tuberculosis(MTB) was developed. This cellular system was used to assess the interaction of MTB-infected monocytes and T cells from dually infected HIV-1/TB patients with pulmonary tuberculosis (TB). Subjects with higher induction of HIV-1 gag/pol mRNA expression after MTB stimulation had increased MTB-specific T cell IFN-γ and TNF-α production. Lack of HIV-1 mRNA induction did not correlate with increased induction of regulatory T cells (T-reg) as measured by MTB-induced Foxp3 mRNA. HIV-1 induction did not significantly correlate with clinical parameters including plasma HIV-1 viral load or CD4+T cell count. These data model MTB-induced HIV-1 replication at the microenvironment of MTB reactivation/infection. The data suggest that the magnitude of MTB-specific T cell responses drives local viral pathogenesis regardless of the stage of HIV-1 disease as reflected by plasma viral load or CD4+T cell count. [ABSTRACT FROM AUTHOR]

HIV-1 is taken up by dendritic cells (DC) and degradation is detectable within a few hours. Little is known about how rapidly HIV-peptide-loaded MHC-II complexes appear on the surface of DC, however. A key impediment to the detailed understanding of MHC-II antigen presentation of HIV-1 has been the lack of good tools to quantitatively measure antigen presentation. We have developed HIV-1-gag p24 and reverse transcriptase (RT)-specific CD4T cell hybridomas that demonstrate high sensitivity and specificity to detect HIV-1 antigens presented by MHC-II on human DC. We demonstrate that ex vivoprimary blood myeloid DC (mDC) and monocyte-derived DC (MDDC) presented HIV-1 peptides on MHC-II molecules within 2 h of exposure to virions. HIV-1 was degraded in a compartment requiring acidification for processing and then was loaded onto newly synthesized MHC-II molecules for presentation. [ABSTRACT FROM AUTHOR]