TB-IRIS after initiation of antiretroviral therapy is associated with expansion of preexistent Th1 responses against Mycobacterium tuberculosis antigens
R Vignesh, N Kumarasamy, A Lim… - JAIDS Journal of …, 2013 - journals.lww.com
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2013•journals.lww.com
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 …
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 …
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.
Lippincott Williams & Wilkins