title: Lower Pre-Treatment T Cell Activation in Early- and Late-Onset Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome.
abstract: BACKGROUND
  Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The role of disturbed T cell reconstitution in TB-IRIS is not well understood. We investigated T cell activation and maturation profiles in patients who developed TB-IRIS at different intervals during ART.
  
  
  METHODS
  Twenty-two HIV-TB patients who developed early-onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS. Flow cytometry analysis was performed on fresh blood, drawn before and after ART initiation and during TB-IRIS events. T cell activation and maturation was measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27 antibodies.
  
  
  RESULTS
  CD8+ T cell activation before ART was decreased in both early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB-IRIS patients compared to non-IRIS controls. After ART initiation, the observed differences in T cell activation disappeared. During late-onset, but not early-onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and CD8+ T cell populations (p≤0.028).
  
  
  CONCLUSIONS
  Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by an over-activated CD8+ T cell compartment. Late- but not early-onset TB-IRIS was characterized by a more terminally differentiated T cell phenotype.
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Odin
authors.initials: O
authors.lastname: Goovaerts
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Jennes
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Centre de Recherches Médicales de Lambaréné (CERMEL), Albert Schweitzer Hospital, Lambarene, Gabon; Institut für Tropenmedizin, Universität Tübingen, Tübingen, Germany.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Massinga-Loembé
authors.affiliation: Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ondoa
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Ceulemans
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Vereecken
authors.affiliation: Department of Medicine, Mulago Hospital, Kampala, Uganda; Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda; Infectious Diseases Network for Treatment and Research in Africa (INTERACT), Kampala, Uganda.
authors.forename: William
authors.initials: W
authors.lastname: Worodria
authors.affiliation: Department of Medicine, Mulago Hospital, Kampala, Uganda; Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
authors.affiliation: Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Epidemiology and Social Medicine, University of Antwerp, Antwerp, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Colebunders
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Kestens
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006801:Humans; D054019:Immune Reconstitution Inflammatory Syndrome / Q000209:etiology*; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy; D019562:Viral Load