Type 1 helper T cells and FoxP3-positive T cells in HIV-tuberculosis-associated immune reconstitution inflammatory syndrome.

RATIONALE: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) induced by combination antiretroviral therapy (cART) has been attributed to dysregulated expansion of tuberculin PPD-specific IFN-gamma-secreting CD4(+) T cells. OBJECTIVES: To investigate the role of type 1 helper T cell expansions and regulatory T cells in HIV-TB IRIS. METHODS: Longitudinal and cross-sectional studies of Mycobacterium tuberculosis-specific IFN-gamma enzyme-linked immunospot responses and flow cytometric analysis of blood cells from a total of 129 adults with HIV-1-associated tuberculosis, 98 of whom were prescribed cART. MEASUREMENTS AND MAIN RESULTS: In cross-sectional analysis the frequency of IFN-gamma-secreting T cells recognizing early secretory antigenic target (ESAT)-6, alpha-crystallins 1 and 2, and PPD of M. tuberculosis was higher in patients with TB-IRIS than in similar patients treated for both HIV-1 and tuberculosis who did not develop IRIS (non-IRIS; P

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

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.

Effect of HIV-1 infection on T-Cell-based and skin test detection of tuberculosis infection.

RATIONALE: Two forms of the IFN-gamma release assay (IFNGRA) to detect tuberculosis infection are available, but neither has been evaluated in comparable HIV-infected and uninfected persons in a high tuberculosis incidence environment. OBJECTIVE: To compare the ability of the T-SPOT.TB (Oxford Immunotec, Abingdon, UK), QuantiFERON-TB Gold (Cellestis, Melbourne, Australia), and Mantoux tests to identify latent tuberculosis in HIV-infected and uninfected persons. METHODS: A cross-sectional study of 160 healthy adults without active tuberculosis attending a voluntary counseling and testing center for HIV infection in Khayelitsha, a deprived urban South African community with an HIV antenatal seroprevalence of 33% and a tuberculosis incidence of 1,612 per 100,000. MEASUREMENTS AND MAIN RESULTS: One hundred and sixty (74 HIV(+) and 86 HIV(-)) persons were enrolled. A lower proportion of Mantoux results was positive in HIV-infected subjects compared with HIV-uninfected subjects (p < 0.01). By contrast, the proportion of positive IFNGRAs was not significantly different in HIV-infected persons for the T-SPOT.TB test (52 vs. 59%; p = 0.41) or the QuantiFERON-TB Gold test (43 and 46%; p = 0.89). Fair agreement between the Mantoux test (5- and 10-mm cutoffs) and the IFNGRA was seen in HIV-infected people (kappa = 0.52-0.6). By contrast, poor agreement between the Mantoux and QuantiFERON-TB Gold tests was observed in the HIV-uninfected group (kappa = 0.07-0.30, depending on the Mantoux cutoff). The pattern was similar for T-SPOT.TB (kappa = 0.18-0.24). INTERPRETATION: IFNGRA sensitivity appears relatively unimpaired by moderately advanced HIV infection. However, agreement between the tests and with the Mantoux test varied from poor to fair. This highlights the need for prospective studies to determine which test may predict the subsequent risk of tuberculosis.