Hong Jung Joo, Amancha Praveen K, Rogers Kenneth A, Courtney Cynthia L, Havenar-Daughton Colin, Crotty Shane, Ansari Aftab A, Villinger Francois
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329; and.
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
J Immunol. 2014 Jul 15;193(2):797-806. doi: 10.4049/jimmunol.1400749. Epub 2014 Jun 6.
We have investigated the dynamics of germinal center (GC) formation in lymphoid tissues following acute SIV infection. SIV induces a marked follicular hyperplasia, associated with an aberrant accumulation of nonproliferating T follicular helper cells within GCs, but with an abundance of cells producing IL-21, demonstrating that the mechanisms involved for these two events appear independent. IL-21-stimulated T follicular helper cells are considered a critical element for GC formation, a physiological process that seems dysregulated and excessive during HIV/SIV infection, contributing to lymphoid pathogenesis. However, the data suggest that the kinetics by which such GCs are formed may be an important predictor of the host-pathogen equilibrium, as early GC hyperplasia was associated with better control of viral replication. In contrast, monkeys undergoing fast disease progression upon infection exhibited an involution of GCs without local IL-21 production in GCs. These results provide important clues regarding GC-related hyperimmune responses in the context of disease progression within various individuals during HIV/SIV infection and may open novel therapeutic avenues to limit lymphoid dysfunction, postinfection.
我们研究了急性SIV感染后淋巴组织中生发中心（GC）形成的动力学。SIV诱导明显的滤泡增生，这与GC内非增殖性滤泡辅助性T细胞的异常积累有关，但同时也有大量产生IL-21的细胞，这表明这两个事件所涉及的机制似乎是独立的。IL-21刺激的滤泡辅助性T细胞被认为是GC形成的关键因素，GC形成是一个生理过程，在HIV/SIV感染期间似乎失调且过度，导致淋巴组织发病机制。然而，数据表明，这些GC形成的动力学可能是宿主-病原体平衡的重要预测指标，因为早期GC增生与更好地控制病毒复制有关。相反，感染后疾病进展迅速的猴子表现出GC退化，且GC内无局部IL-21产生。这些结果为HIV/SIV感染期间不同个体疾病进展背景下与GC相关的超免疫反应提供了重要线索，并可能为限制感染后淋巴组织功能障碍开辟新的治疗途径。
