Type 1 Helper T Cells and FoxP3-positive T Cells in HIV–Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome
Year: 2008
Type: article
Study design: Observational Study
Abstract: Rationale 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-γ–secreting CD4+ T cells. Objectives 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-γ 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. Measurements and Main Results In cross-sectional analysis the frequency of IFN-γ–secreting T cells recognizing early secretory antigenic target (ESAT)-6, α-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 ≤ 0.03). The biggest difference was in the recognition of α-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-γ–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.
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Wellcome Trust, Medical Research Council
Awards: Immunological investigation of pericardial tuberculosis, Understanding tuberculosis in Cape Town, South Africa, Clinical proteomic and genomic characterisation of the immune reconstitution inflammatory syndrome in HIV-associated tuberculosis, Phenotypic and Genotypic Characterisation of Clinical Strains of Mycobacterium tuberculosis Causing Pulmonary and Extra-Pulmonary Disease in Children., G76681233, Evaluation of the predictive value for tuberculosis of T cell based assays vs tuberculosis skin test in HIV infected persons on combination antiretroviral therapy: a prospective study.
OpenAlex ID: W2160552059