title: Skewing of the CD4(+) T-cell pool toward monofunctional antigen-specific responses in patients with immune reconstitution inflammatory syndrome in The Gambia.
abstract: 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.
authors: Vaccinology Theme, Medical Research Council Unit, Fajara, The Gambia.
authors: Harry
authors: H
authors: Wilson
authors: Bouke C
authors: BC
authors: de Jong
authors: Kevin
authors: K
authors: Peterson
authors: Assan
authors: A
authors: Jaye
authors: Beate
authors: B
authors: Kampmann
authors: Martin O C
authors: MO
authors: Ota
authors: Jayne S
authors: JS
authors: Sutherland
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D005714:Gambia; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000276:immunology*; D007963:Leukocytes, Mononuclear; D008137:Longitudinal Studies; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D044966:Anti-Retroviral Agents; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D014373:Tuberculin
keywords: HIV; West Africa; immune reconstitution inflammatory syndrome; polyfunctional T cells; tuberculosis