Lund Frances E, Hollifield Melissa, Schuer Kevin, Lines J Louise, Randall Troy D, Garvy Beth A
Trudeau Institute, Saranac Lake, NY 12983, USA.
J Immunol. 2006 May 15;176(10):6147-54. doi: 10.4049/jimmunol.176.10.6147.
B cell-deficient mice are susceptible to infection by Pneumocystis carinii f. sp. muris (PC). To determine whether this susceptibility is due to a requirement for B cells to prime T cells, we compared CD4 T cell responses to PC in bone marrow chimeric mice that express MHC class II (MHCII) on all APCs (wild-type (WT) chimeras) and in bone marrow chimeric mice that express MHCII on all APCs except B cells (MHCII(-/-) chimeras). Although PC was rapidly cleared by WT chimeric mice, PC levels remained high in chimeric mice that lacked MHCII on B cells. In addition, although T cells were primed in the draining lymph nodes of MHCII(-/-) chimeric mice, the number of activated CD4 T cells infiltrating the lungs of these mice was reduced relative to the number in the lungs of WT chimeras. We also adoptively transferred purified CD4 T cells from the draining lymph nodes of PC-infected normal or B cell-deficient mice into SCID mice. Mice that received CD4 cells from normal mice were able to mount a response to infection in the lungs and clear PC. However, mice that received CD4 cells from B cell-deficient mice had a delayed T cell response in the lungs and failed to control the infection. These data indicate that B cells play a vital role in generation of CD4(+) memory T cells in response to PC infection in the lungs.
B细胞缺陷型小鼠易受卡氏肺孢子虫小鼠变种(PC)感染。为了确定这种易感性是否是由于B细胞对T细胞启动的需求,我们比较了在所有抗原呈递细胞(APC)上表达MHC II类分子(MHCII)的骨髓嵌合小鼠(野生型(WT)嵌合体)和除B细胞外所有APC上表达MHCII的骨髓嵌合小鼠(MHCII(-/-)嵌合体)中CD4 T细胞对PC的反应。尽管WT嵌合小鼠能迅速清除PC,但B细胞上缺乏MHCII的嵌合小鼠体内PC水平仍很高。此外,尽管MHCII(-/-)嵌合小鼠的引流淋巴结中T细胞被启动,但相对于WT嵌合体小鼠肺部,浸润这些小鼠肺部的活化CD4 T细胞数量减少。我们还将来自PC感染的正常或B细胞缺陷型小鼠引流淋巴结的纯化CD4 T细胞过继转移到SCID小鼠体内。接受正常小鼠CD4细胞的小鼠能够在肺部对感染产生反应并清除PC。然而,接受B细胞缺陷型小鼠CD4细胞的小鼠肺部T细胞反应延迟,无法控制感染。这些数据表明,B细胞在肺部对PC感染产生CD4(+)记忆T细胞的过程中起着至关重要的作用。