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.
*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.
Correspondence to: Ramachandran Vignesh, PhD, Infectious Diseases Laboratory, YR Gaitonde Centre for AIDS Research and Education, VHS, Taramani, Chennai 600113, India (e-mail: firstname.lastname@example.org).
The authors have no funding or conflicts of interest to disclose.
Presented at the 23rd Annual Australasian Society for HIV Medicine Conference, September 26–28, 2011, Canberra, Australia, Paper 323; and 19th Conference on Retroviruses and Opportunistic Infections, March 5–8, 2012, Seattle, WA, Poster 940.
Received March 18, 2013
Accepted June 03, 2013