Skewing of the CD4+T-Cell Pool Toward Monofunctional Antigen-Specific Responses in Patients With Immune Reconstitution Inflammatory Syndrome in The Gambia

Background. A common complication of starting antiretroviral therapy (ART) for human immunodeficiency virus (HIV) is the development of immune reconstitution inflammatory syndrome (IRIS) in approximately 25% of patients. Despite similarities with paradoxical reactions to tuberculosis and reversal re...

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Bibliographic Details
Published in:Clinical infectious diseases 2013-08, Vol.57 (4), p.594-603
Main Authors: Wilson, Harry, de Jong, Bouke C., Peterson, Kevin, Jaye, Assan, Kampmann, Beate, Ota, Martin O. C., Sutherland, Jayne S.
Format: Article
Language:English
Subjects:
Adult
Anti-Retroviral Agents - adverse effects
Anti-Retroviral Agents - therapeutic use
Antigens
Antigens, Bacterial - immunology
Antiretroviral drugs
Antiretrovirals
Art therapy
Arts
Bacterial Proteins - immunology
Biological and medical sciences
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Cohort Studies
Cytokines
Cytokines - biosynthesis
Female
Flow Cytometry
Gambia
General aspects
Glycoproteins
HIV
HIV Infections - complications
HIV Infections - drug therapy
HIV Infections - immunology
HIV/AIDS
Human immunodeficiency virus
Humans
Immune Reconstitution Inflammatory Syndrome - immunology
Immune system
Immunopathology
Infectious diseases
Leukocytes, Mononuclear
Longitudinal Studies
Male
Medical sciences
T cell receptors
T lymphocytes
T-Lymphocyte Subsets - immunology
Tuberculin
Tuberculin - immunology
Tuberculosis
Tuberculosis - immunology
Tumor necrosis factors
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Summary:Background. A common complication of starting antiretroviral therapy (ART) for human immunodeficiency virus (HIV) is the development of immune reconstitution inflammatory syndrome (IRIS) in approximately 25% of patients. Despite similarities with paradoxical reactions to tuberculosis and reversal reactions in leprosy, the exact mechanisms, and therefore potential determinants, of IRIS are still unknown. Methods. In this longitudinal cohort study, we analyzed 20 patients who developed IRIS following initiation of ART and 16 patients who did not, matched for ART time point. Peripheral blood mononuclear cells were stimulated overnight with a positive control antigen and 2 tuberculosis-specific antigens (purified protein derivative [PPD] and ESAT-6/CFP10), followed by polychromatic flow cytometry for analysis of cytokine production from CD4 + and CD8 + T cells. Results. Responses to PPD were significantly higher in IRIS patients compared to controls during the IRIS time point, but CD4 + and CD8 + T-cell responses to the positive control stimulation were significantly lower in IRIS patients at all time points. Furthermore, whereas control patients had rejuvenated polyfunctional T-cell responses by 3 months after ART, IRIS patients were strikingly monofunctional (generally interferon γ alone), even up to 6 months of ART in response to all stimulations. Conclusions. Our findings suggest that the peripheral T-cell responses to the underlying pathogen are exaggerated in IRIS patients but that the overall quality of the peripheral T-cell pool is significantly reduced compared to non-IRIS patients. Furthermore, these effects are apparent at least up to 3 months after cessation of IRIS.
ISSN:1058-4838
1537-6591
DOI:10.1093/cid/cit285