Dendritic cell recruitment in response to skin antigen tests in HIV-1-infected individuals correlates with the level of T-cell infiltration.

Abstract

To study whether in-vivo recruitment of dendritic cells in response to antigen administration in the skin is altered during HIV-1 infection. Skin punch biopsies were collected from HIV-1-positive as well as seronegative individuals at 48 h after intradermal injection of inactivated antigens of mumps virus, Candida albicans, or purified protein derivate (PPD) from Mycobacterium tuberculosis. Cryosections were analyzed by in-situ staining and computerized imaging. Control skin biopsies showed that there was no difference in the number of skin-resident dendritic cells between seronegative and HIV-1-positive individuals. Antigen injection resulted in substantial infiltration of dendritic cells compared to the frequencies found in donor-matched control skin. In HIV-1-positive individuals, CD123(+)/CD303(+) plasmacytoid dendritic cells and CD11c myeloid dendritic cells, including the CD141(+) cross-presenting subset, were recruited at lower levels compared to healthy controls in response to PPD and mumps but not C. albicans. The level of dendritic cell recruitment correlated with the frequencies of T cells infiltrating the respective antigen sites. Ki67(+) cycling T cells at the injection sites were much more frequent in response to each of the antigens in the HIV-1-positive individuals, including those with AIDS, compared to healthy controls. Multiple dendritic cell subsets infiltrate the dermis in response to antigen exposure. There was no obvious depletion or deficiency in mobilization of dendritic cells in response to antigen skin tests during chronic HIV-1 infection. Instead, the levels of antigen-specific memory T cells that accumulate at the antigen site may determine the level of dendritic cell infiltration.