title: Type 1 helper T cells and FoxP3-positive T cells in HIV-tuberculosis-associated immune reconstitution inflammatory syndrome.
abstract: BACKGROUND
  Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) induced by combination antiretroviral therapy (cART) has been attributed to dysregulated expansion of tuberculin PPD-specific IFN-gamma-secreting CD4(+) T cells.
  
  
  OBJECTIVE
  To investigate the role of type 1 helper T cell expansions and regulatory T cells in HIV-TB IRIS.
  
  
  METHODS
  Longitudinal and cross-sectional studies of Mycobacterium tuberculosis-specific IFN-gamma enzyme-linked immunospot responses and flow cytometric analysis of blood cells from a total of 129 adults with HIV-1-associated tuberculosis, 98 of whom were prescribed cART.
  
  
  RESULTS
  In cross-sectional analysis the frequency of IFN-gamma-secreting T cells recognizing early secretory antigenic target (ESAT)-6, alpha-crystallins 1 and 2, and PPD of M. tuberculosis was higher in patients with TB-IRIS than in similar patients treated for both HIV-1 and tuberculosis who did not develop IRIS (non-IRIS; P <or= 0.03). The biggest difference was in the recognition of alpha-crystallin molecules: peptide mapping indicated a polyclonal response. Flow cytometric analysis indicated equal proportions of CD4(+) and CD8(+) cells positive for activation markers HLA-DR and CD71 in both patients with TB-IRIS and non-IRIS patients. The percentage of CD4(+) cells positive for FoxP3 (Forkhead box P3) was low in both groups (TB-IRIS, 5.3 +/- 4.5; non-IRIS, 2.46 +/- 2.46; P = 0.13). Eight weeks of longitudinal analysis of patients with tuberculosis who were starting cART showed dynamic changes in antigen-specific IFN-gamma-secreting T cells in both the TB-IRIS and non-IRIS groups: the only significant trend was an increased response to PPD in the TB-IRIS group (P = 0.041).
  
  
  CONCLUSIONS
  There is an association between helper T-cell type 1 expansions and TB-IRIS, but the occurrence of similar expansions in non-IRIS brings into question whether these are causal. The defect in immune regulation responsible for TB-IRIS remains to be fully elucidated.
authors.affiliation: F.R.C.P., Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory 7925, South Africa. r.j.wilkinson@imperial.ac.uk.
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.forename: Katalin Andrea
authors.initials: KA
authors.lastname: Wilkinson
authors.forename: Molebogeng Xheeda
authors.initials: MX
authors.lastname: Rangaka
authors.forename: Keira
authors.initials: K
authors.lastname: Skolimowska
authors.forename: Kerryn
authors.initials: K
authors.lastname: van Veen
authors.forename: Musaed
authors.initials: M
authors.lastname: Abrahams
authors.forename: Ronnett
authors.initials: R
authors.lastname: Seldon
authors.forename: Dominique J
authors.initials: DJ
authors.lastname: Pepper
authors.forename: Kevin
authors.initials: K
authors.lastname: Rebe
authors.forename: Priscilla
authors.initials: P
authors.lastname: Mouton
authors.forename: Gilles
authors.initials: G
authors.lastname: van Cutsem
authors.forename: Mark Patrick
authors.initials: MP
authors.lastname: Nicol
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
authors.forename: Robert John
authors.initials: RJ
authors.lastname: Wilkinson