Type 1 Helper T Cells and FoxP3-positive T Cells in HIV-Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome

被引：121

作者：

Meintjes, Graerne ^{[1
,2
,3
]}

Wilkinson, Katalin Andrea ^{[1
,2
,4
]}

Rangaka, Molebogeng Xheedla ^{[1
,2
]}

Skolimowska, Keira ^{[3
,5
]}

Van Veen, Kerryn ^{[1
,2
]}

Abrahams, Musaed ^{[6
]}

Seldon, Ronnett ^{[1
,2
]}

Pepper, Dorninique J. ^{[1
,2
,3
]}

Rebe, Kevin ^{[3
]}

Mouton, Priscilla ^{[1
,2
]}

Van Cutsem, Gilles ^{[7
]}

Nicol, Mark Patrick ^{[1
,2
]}

Maartens, Gary ^{[1
,2
,8
]}

Wilkinson, Robert John ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa

[2] Univ Cape Town, Dept Med, ZA-7925 Cape Town, South Africa

[3] GF Jooste Hosp, Manenberg, South Africa

[4] Natl Inst Med Res, London NW7 1AA, England

[5] Univ London Imperial Coll Sci Technol & Med, Div Med, London, England

[6] Prov Adm Western Cape, Khayelitsha, South Africa

[7] Med Sans Frontieres, Khayelitsha, South Africa

[8] Univ Cape Town, Dept Med, Div Clin Pharmacol, ZA-7925 Cape Town, South Africa

来源：

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE | 2008年 / 178卷 / 10期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

tuberculosis; HIV; immune reconstitution inflammatory syndrome; FoxP3; type 1 helper T cells;

D O I：

10.1164/rccm.200806-858OC

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

Rationale: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) induced by combination antiretroviral therapy (cART) has been attributed to dysregulated expansion of tuberculin IPPD-specific IFN-gamma-secreting CD4(+) T cells. Objectives: To investigate the role of type I 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. Measurements and Main 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 <= 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-DIR 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.

引用

页码：1083 / 1089

页数：7

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