Human immunodeficiency virus gp120 downregulates CD1d cell surface expression.

CD1d is an MHC class I-like surface molecule that presents endogenous glycoplipid antigens. The effect of HIV infection on CD1d surface expression has not yet been reported. FACS analysis revealed significantly lower levels of CD1d on CD14(+) monocytes from HIV-infected subjects compared to HIV-infected subjects on HAART and healthy controls. CD1d expression correlated inversely with viral load in infected individuals. CD1d surface expression on human cell lines was downregulated after infection with M-tropic HIV, T-tropic HIV, or after exposure to HIV gp120 in vitro. These data suggest that CD1d-mediated responses are altered during HIV infection and may thus contribute to the global immunodeficiency seen in these patients.

CD4+CD28-T cells are expanded in sarcoidosis.

BACKGROUND AND AIM: A subset of CD4+ lymphocytes lacking CD28, an important costimulatory molecule, is increased in certain inflammatory conditions. However, studies have not directly studied CD4+CD28-lymphocytes in patients with chronic sarcoidosis. The aim of this study was to further characterize the CD4+CD28-T cell population in patients with sarcoidosis, particularly those with active disease. METHODS: Seventeen patients with chronic sarcoidosis and 15 blood donors were studied. Bronchoalveolar lavage cells were available for paired analysis in seven sarcoid patients. In 4 sarcoid patients, adequate sample was available for intracellular cytokine analysis by flow cytometry. IFN-gamma production in plasma and BAL was determined by ELISA and cytometric bead array analysis and compared to previously studied controls. RESULTS: Peripheral blood from patients with sarcoidosis had a significantly higher proportion of CD4+CD28- cells compared with healthy donors. A higher percentage of CD4+CD28- cells was evident in the BAL relative to peripheral blood in patients with active sarcoid. IFN-gamma levels were greater both in the plasma and concentrated BAL fluid of sarcoid subjects compared to controls. The majority of IFN-gamma and TNF-alpha producing lymphocytes were CD28+ in both healthy blood donors and sarcoid subjects. CONCLUSIONS: CD4+CD28- cells are increased in the peripheral blood and lungs of patients with sarcoidosis requiring treatment. These cells may contribute to the inflammatory response; however, they are not major contributors of IFN-gamma or TNF-alpha.

Macrophages exposed to lymphotropic and monocytotropic HIV induce similar CTL responses despite differences in productive infection.

Macrophages are accessory cells that are vulnerable to infection by HIV-1. HTLV-IIIB, a lymphotropic strain of HIV, infects macrophages poorly resulting in either no or low levels of virus expression compared to high levels of productive infection after exposure of macrophages to the monocytotropic HIV strain Ada-M. Whether this results in an impaired ability of HTLV-IIIB-exposed macrophages to initiate protective cytotoxic T lymphocyte (CTL) immune responses against these strains is not well defined. We investigated the ability of monocyte-derived macrophages (MDM) exposed to lymphotropic and monocytotropic HIV strains to initiate primary CTL responses in vitro. MDM exposed to HTLV-IIIB induced a specific primary CTL response that was comparable to MDM exposed to the monocytotropic strain Ada-M despite marked differences in productive HIV infection in MDM between the two strains. CTL generated in this model were MHC-restricted, strain-specific, and CD8+. These data demonstrate that high levels of productive HIV infection in accessory cells are not a prerequisite for the generation of a primary CTL response, suggesting a novel immunologic interaction between MDM and lymphotropic HIV strains.