4.7 Article

Elevated frequencies of highly activated CD4+ T cells in HIV+ patients developing immune reconstitution inflammatory syndrome

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BLOOD
卷 116, 期 19, 页码 3818-3827

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AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-05-285080

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  1. National Institute of Allergy and Infectious Diseases of the National Institutes of Health (Bethesda, MD)
  2. National Cancer Institute, National Institutes of Health [HHSN261200800001E]

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Immune reconstitution inflammatory syndrome (IRIS) is a considerable problem in the treatment of HIV-infected patients. To identify immunologic correlates of IRIS, we characterized T-cell phenotypic markers and serum cytokine levels in HIV patients with a range of different AIDS-defining illnesses, before and at regular time points after initiation of anti-retroviral therapy. Patients developing IRIS episodes displayed higher frequencies of effector memory, PD-1(+), HLA-DR+, and Ki67(+) CD4(+) T cells than patients without IRIS. Moreover, PD-1(+) CD4(+) T cells in IRIS patients expressed increased levels of LAG-3, CTLA-4, and ICOS and had a Th1/Th17 skewed cytokine profile upon polyclonal stimulation. Elevated PD-1 and Ki67 expression was also seen in regulatory T cells of IRIS patients. Furthermore, IRIS patients displayed higher serum interferon-gamma, compared with non-IRIS patients, near the time of their IRIS events and higher serum interleukin-7 levels, suggesting that the T-cell populations are also exposed to augmented homeostatic signals. In conclusion, our findings indicate that IRIS appears to be a predominantly CD4-mediated phenomenon with reconstituting effector and regulatory T cells showing evidence of increased activation from antigenic exposure. These studies are registered online at http://clinicaltrials.gov as NCT00557570 and NCT00286767. (Blood. 2010;116(19):3818-3827)

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