Association between tuberculin skin test reactivity, the memory CD4 cell subset, and circulating FoxP3-expressing cells in HIV-infected persons.

ABSTRACT

BACKGROUND: Lack of reactivity to the tuberculin skin test (TST) is widely observed in individuals with advanced human immunodeficiency virus type 1 (HIV-1) infection. METHODS: Biopsy specimens from the TST reaction site and from skin not infiltrated with purified protein derivative were obtained from 15 HIV-1-infected and 23 uninfected persons who did not have active tuberculosis and who were from a community in which the incidence of tuberculosis was very high. Histologic sections (size, 8 mum) were immunohistochemically stained for CD4, CD8, CD28, CD45RA, CD45RO, CD62L, CD1a, human leukocyte antigen (HLA)-DR, granulysin, interferon-gamma, and FoxP3 and were analyzed by single-cell in situ digital imaging. Peripheral blood mononuclear cells were analyzed using a fluorescence-activated cell sorter. RESULTS: Biopsy specimens obtained from TST-reactive skin of HIV-1-infected persons demonstrated fewer CD4(+) T cells at the TST site (P = .36) but more HLA-DR(+) T cells (P = .037) than did such biopsy specimens obtained from HIV-1-uninfected persons. Among HIV-1-infected persons, the total number of cells (P = .008) and numbers of CD45RO(+) memory T cells (P = .003) were significantly higher in TST-reactive persons than in TST-unreactive persons. For HIV-1-infected persons, TST induration was inversely correlated with the numbers of FoxP3(+) T cells in the blood (P = .026) but was unrelated to the number of circulating CD4(+) T cells. CONCLUSIONS: For HIV-1 infected persons, the TST depends on memory T cells and is more strongly associated with the numbers of circulating FoxP3(+)CD4(+) T cells than with the total number of CD4(+) T cells.