Barros Nicolas, Sanchez Cesar A, White A Clinton, Bauer Allison, Woll Fernando, Graviss Edward A, Seas Carlos, Gotuzzo Eduardo, Montes Martin
Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, 15102 Lima, Peru.
Division of Infectious Diseases, Indiana University, Indianapolis, IN 46202, USA.
J Mol Clin Med. 2025;8(1). doi: 10.31083/JMCM25012. Epub 2025 Feb 5.
Combination antiretroviral therapy (cART) can suppress human immunodeficiency virus (HIV-1) replication, but some patients develop worsening of co-infections, termed immune reconstitution inflammatory syndrome. Regulatory T cells (Tregs) are a population of CD4 T cells that modulate immune responses. We hypothesized that immune reconstitution inflammatory syndrome (IRIS) is associated with Tregs dysfunction.
We prospectively enrolled antiretroviral naive HIV patients with co-infection with (MTB; N = 26) or controls with no prior opportunistic infection (N = 10). We prospectively measured HIV viral load, CD4 T cell count, regulatory T cell (CD4, CD127, Foxp) proportion, and Interferon- (IFN-) response to MTB peptides before and after initiation of combination antiretroviral therapy.
Eleven of the MTB patients developed IRIS; 15 did not. IRIS patients had a lower proportion of Tregs at baseline compared to no-IRIS patients (HIV/no-OI and HIV/MTB no-IRIS), but the difference did not reach statistical significance (IRIS: 9.6 [5.3-11.2]; no-IRIS: 13.9 [7.6-22.5] = 0.066). After 2 weeks of cART the proportion of Tregs was significantly lower in HIV/MTB IRIS patients (HIV/MTB IRIS: 9.8 [6.6-13.6], HIV/MTB no-IRIS: 15.8 [11.1-18.8]. The antigen-specific IFN- production was greater in the patients who developed IRIS compared with those who did not develop IRIS.
IRIS patients had a lower proportion of Tregs and more marked IFN- production, suggesting that Tregs may be responsible for suppressing the antigen-specific inflammatory response.
联合抗逆转录病毒疗法（cART）可抑制人类免疫缺陷病毒（HIV-1）复制，但部分患者会出现合并感染恶化的情况，即免疫重建炎症综合征。调节性T细胞（Tregs）是一类可调节免疫反应的CD4 T细胞亚群。我们推测免疫重建炎症综合征（IRIS）与Tregs功能障碍有关。
我们前瞻性纳入了未接受过抗逆转录病毒治疗且合并结核分枝杆菌（MTB；n = 26）感染的HIV患者或无既往机会性感染的对照者（n = 10）。我们前瞻性地检测了联合抗逆转录病毒治疗开始前后的HIV病毒载量、CD4 T细胞计数、调节性T细胞（CD4、CD127、Foxp）比例以及对MTB肽段的干扰素-γ（IFN-γ）反应。
26例MTB患者中有11例发生了IRIS；15例未发生。与未发生IRIS的患者（HIV/无机会性感染和HIV/MTB未发生IRIS）相比，IRIS患者基线时Tregs比例较低，但差异未达到统计学意义（IRIS：9.6 [5.3 - 11.2]；未发生IRIS：13.9 [7.6 - 22.5]，P = 0.066）。cART治疗2周后，HIV/MTB IRIS患者的Tregs比例显著低于HIV/MTB未发生IRIS的患者（HIV/MTB IRIS：9.8 [6.6 - 13.6]，HIV/MTB未发生IRIS：15.8 [11.1 - 18.8]）。发生IRIS的患者与未发生IRIS的患者相比，抗原特异性IFN-γ产生量更高。
IRIS患者的Tregs比例较低且IFN-γ产生更为明显，提示Tregs可能负责抑制抗原特异性炎症反应。
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