title: TB-IRIS after initiation of antiretroviral therapy is associated with expansion of preexistent Th1 responses against Mycobacterium tuberculosis antigens.
abstract: BACKGROUND
  The role of T-cell responses against Mycobacterium tuberculosis antigens in tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is unclear.
  
  
  METHODS
  Peripheral blood mononuclear cells from 45 HIV patients with treated TB, of whom 12 developed TB-IRIS, were collected at weeks 0, 2, and 6 of antiretroviral therapy (ART). Production of interferon-gamma (IFN-γ) and interleukin-2 by T cells after stimulation with purified protein derivative (PPD) or early secretory antigenic target-6 (ESAT-6) and T-cell expressions of CCR5 and CXCR3 were assessed by flow cytometry. IFN-γ and CXCL10 were assayed by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  TB-IRIS patients had higher proportions of PPD- and ESAT-6-reactive IFN-γ⁺CD4⁺ and CD3⁺CD4⁻ T cells at weeks 0, 2, and 6. IFN-γ levels were also higher in peripheral blood mononuclear cell culture supernatants at all times with PPD but only at weeks 2 and 6 with ESAT-6. There were few differences for interleukin-2. CXCL10 levels in supernatants after PPD and ESAT-6 stimulation were only higher at week 6. CXCR3⁺/CCR5⁺CD4⁺ T cells were higher at week 2, and CCR5⁺CD4⁺ T cells were higher at week 6.
  
  
  CONCLUSIONS
  TB-IRIS is associated with Th1 responses against M. tuberculosis antigens by CD4⁺ and CD3⁺CD4⁻ T cells that are present before ART and amplified afterward. It is unclear if these cause immunopathology or reflect a high pathogen load.
authors.affiliation: *Infectious Diseases Laboratory, YR Gaitonde Centre for AIDS Research and Education (YRG CARE), Chennai, India; †School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia; ‡Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; §HIV Prevention Research, Beth Israel Deaconess Medical Center, Boston, MA; ‖Division of Infectious Diseases, University of California, San Diego, CA; and ¶Medical Centre, Centre for AIDS Research and Education, Chennai, India.
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Vignesh
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.forename: Andrew
authors.initials: A
authors.lastname: Lim
authors.forename: Suniti
authors.initials: S
authors.lastname: Solomon
authors.forename: Kailapuri G
authors.initials: KG
authors.lastname: Murugavel
authors.forename: Pachamuthu
authors.initials: P
authors.lastname: Balakrishnan
authors.forename: Sunil S
authors.initials: SS
authors.lastname: Solomon
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Mayer
authors.forename: Chinnambedu R
authors.initials: CR
authors.lastname: Swathirajan
authors.forename: Ezhilarasi
authors.initials: E
authors.lastname: Chandrasekaran
authors.forename: Ambrose
authors.initials: A
authors.lastname: Pradeep
authors.forename: Selvamuthu
authors.initials: S
authors.lastname: Poongulali
authors.forename: Constance A
authors.initials: CA
authors.lastname: Benson
authors.forename: Martyn A
authors.initials: MA
authors.lastname: French
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000276:immunology* / Q000503:physiopathology; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000942:Antigens, Bacterial / Q000276:immunology*; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000276:immunology* / Q000503:physiopathology; D007194:India / Q000453:epidemiology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000503:physiopathology
chemical_list: D019380:Anti-HIV Agents; D000942:Antigens, Bacterial; C584933:CCR5 protein, human; D017252:CD3 Complex; C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D007376:Interleukin-2; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D016753:Interleukin-10; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma