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Loss of Preexisting Immunological Memory Among Human Immunodeficiency Virus-Infected Women Despite Immune Reconstitution With Antiretroviral Therapy.
The Journal of Infectious Diseases ( IF 5.0 ) Pub Date : 2019-12-23 , DOI: 10.1093/infdis/jiz678
Archana Thomas 1 , Erika Hammarlund 1 , Lina Gao 2 , Susan Holman 3 , Katherine G Michel 4 , Marshall Glesby 5 , Maria C Villacres 6 , Elizabeth T Golub 7 , Nadia R Roan 8 , Audrey L French 9 , Michael H Augenbraun 3 , Mark K Slifka 1
Affiliation  

BACKGROUND It is unclear if HIV infection results in permanent loss of T cell memory or if it impacts pre-existing antibodies to childhood vaccinations/infections. METHODS We conducted a matched cohort study involving 50 pairs of HIV+ and HIV- women. Total memory T cell responses were measured after anti-CD3 stimulation or after vaccinia virus stimulation to measure T cells elicited after childhood smallpox vaccination. Vaccinia-specific antibodies were measured by ELISA. RESULTS There was no difference between HIV+ and HIV- subjects in terms of CD4+ T cell responses after anti-CD3 stimulation (P=0.19) although HIV+ subjects had significantly higher CD8+ T cell responses (P=0.033). In contrast, there was a significant loss in vaccinia-specific CD4+ T cell memory among HIV+ subjects (P=0.039) whereas antiviral CD8+ T cell memory remained intact (P=1.0). Vaccinia-specific antibodies were maintained indefinitely among HIV- subjects (half-life; infinity, 95%CI, 309 years-infinity) but declined rapidly among HIV+ subjects (half-life; 39 years, 95%CI, 24-108 years, P=0.001). CONCLUSIONS Despite ART-associated improvement in CD4+ T cell counts (nadir CD4 <200 cells/mm3 with >350 cells/mm3 after ART), antigen-specific CD4+ T cell memory to vaccinations/infections that occurred before HIV infection did not recover after immune reconstitution and a previously unrealized decline in pre-existing antibody responses was observed.

中文翻译:


尽管通过抗逆转录病毒治疗进行了免疫重建,但感染人类免疫缺陷病毒的女性仍丧失了原有的免疫记忆。



背景 目前尚不清楚 HIV 感染是否会导致 T 细胞记忆永久丧失,或者是否会影响针对儿童疫苗接种/感染的预先存在的抗体。方法 我们进行了一项配对队列研究,涉及 50 对 HIV 阳性和 HIV 阴性女性。在抗 CD3 刺激后或在牛痘病毒刺激后测量总记忆 T 细胞反应,以测量儿童天花疫苗接种后引发的 T 细胞。通过 ELISA 测量痘苗病毒特异性抗体。结果 尽管 HIV+ 受试者的 CD8+ T 细胞反应显着较高(P=0.033),但 HIV+ 受试者和 HIV- 受试者在抗 CD3 刺激后的 CD4+ T 细胞反应方面没有差异(P=0.19)。相比之下,HIV+受试者中痘苗特异性CD4+T细胞记忆显着丧失(P=0.039),而抗病毒CD8+T细胞记忆保持完整(P=1.0)。痘苗特异性抗体在 HIV- 受试者中无限期地维持(半衰期;无穷大,95% CI,309 年 - 无穷大),但在 HIV+ 受试者中迅速下降(半衰期;39 年,95% CI,24-108 年, P=0.001)。结论 尽管 ART 相关的 CD4+ T 细胞计数有所改善(ART 后最低点 CD4 <200 id=2>350 个细胞/mm3),但免疫重建后对 HIV 感染前发生的疫苗接种/感染的抗原特异性 CD4+ T 细胞记忆并未恢复并且观察到预先存在的抗体反应出现了以前未实现的下降。
更新日期:2019-12-23
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