Moir Susan, Ogwaro Kisani M, Malaspina Angela, Vasquez Joshua, Donoghue Eileen T, Hallahan Claire W, Liu Shuying, Ehler Linda A, Planta Marie A, Kottilil Shyamasundaran, Chun Tae-Wook, Fauci Anthony S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2003 May 13;100(10):6057-62. doi: 10.1073/pnas.0730819100. Epub 2003 May 1.
HIV infection induces a wide array of B cell dysfunctions. We have characterized the effect of plasma viremia on the responsiveness of B cells to CD4(+) T cell help in HIV-infected patients. In HIV-negative donors, B cell proliferation correlated with CD154 expression on activated CD4(+) T cells and with the availability of IL-2, whereas in HIV-infected viremic patients, reduced B cell proliferation was observed despite normal CD154 expression on activated CD4(+) T cells. Reduced triggering of B cells by activated CD4(+) T cells was clearly observed in HIV-infected viremic patients compared with aviremic patients with comparable CD4(+) T cell counts, and a dramatic improvement in B cell function was observed in patients whose plasma viremia was controlled by effective antiretroviral therapy. The degree of B cell dysfunction in viremic patients correlated strongly with the inability of B cells to express CD25 in response to activated CD4(+) T cells, resulting in an inability to mount a normal proliferative response to IL-2. Similar defects in responsiveness to IL-2 were observed in the B cells of HIV-infected viremic patients in the context of B cell receptor stimulation. These data provide new insight into the mechanisms associated with ineffective humoral responses in HIV disease.
HIV感染会引发一系列B细胞功能障碍。我们已经阐明了血浆病毒血症对HIV感染患者中B细胞对CD4(+) T细胞辅助反应性的影响。在HIV阴性供者中，B细胞增殖与活化的CD4(+) T细胞上的CD154表达以及IL-2的可获得性相关，而在HIV感染的病毒血症患者中，尽管活化的CD4(+) T细胞上的CD154表达正常，但仍观察到B细胞增殖减少。与具有可比CD4(+) T细胞计数的无病毒血症患者相比，在HIV感染的病毒血症患者中明显观察到活化的CD4(+) T细胞对B细胞的触发减少，并且在血浆病毒血症通过有效的抗逆转录病毒疗法得到控制的患者中观察到B细胞功能有显著改善。病毒血症患者中B细胞功能障碍的程度与B细胞在响应活化的CD4(+) T细胞时无法表达CD25密切相关，导致无法对IL-2产生正常的增殖反应。在B细胞受体刺激的情况下，在HIV感染的病毒血症患者的B细胞中也观察到对IL-2反应性的类似缺陷。这些数据为与HIV疾病中无效体液反应相关的机制提供了新的见解。
