MHC class II-positive perivascular microglial cells mediate resistance to Cryptococcus neoformans brain infection
MHC class II-positive perivascular microglial cells mediate resistance to Cryptococcus neoformans brain infection
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作者：
Aguirre, K;Miller, S
对中枢神经系统病原体新生隐球菌的获得性耐药性是由主要组织相容性II类(MHC II)分子背景下的抗原启动的CD4(+)T淋巴细胞介导的。在小鼠脑内，实质和血管周围的小胶质细胞可能表达干扰素-γ(干扰素-γ)诱导的MHC-II类标志，从而与CD4(+)T细胞相互作用。如果在适当的MHC环境中遇到抗原，启动的效应T细胞将保留在感染的CNS中，并可能传递信号，增强小胶质细胞的抑菌作用。接种C57BL6/J的小鼠能抵抗通常致命的新生芽孢杆菌的再攻击，但相同处理的同源Abeta(o/o)小鼠(MHC II类缺陷；CD4(+)T细胞缺陷)不能。Abeta(o/o)小鼠也不能像严重联合免疫缺陷(SCID)小鼠(MHC II类完整，淋巴细胞缺陷)那样，通过输注接种C57BL6/J供者的淋巴细胞进行过继免疫。嵌合(C57BL/6J：Abeta(o/o))小鼠可能只在血管周围小胶质细胞上表达II类，与SCID小鼠一样，能够过继免疫对抗新生弧菌的脑感染。相反，可能只在实质小胶质细胞上表达II类基因的嵌合小鼠不能有效地过继免疫对抗新生隐球虫的脑感染。因此，为了介导对感染的抵抗，启动的CD4(+)T细胞必须与靠近脑血管的血管周围可再生的小胶质细胞亚群相互作用。尽管T细胞可能以炎性细胞因子的形式为实质小胶质细胞提供帮助，但这些细胞上II类分子的表达对于抗真菌活性似乎是不必要的。(C)2002年Wiley-Liss，Inc.
Acquired resistance to the CNS pathogen Cryptococcus neoformans is mediated by CD4(+) T lymphocytes primed by exposure to antigen in the context of major histocompatibility class II (MHC II) molecules. In mouse brain, parenchymal and perivascular microglial cells may express interferon-gamma (IFN-gamma)-inducible MHC class II marker and thus interact with CD4(+) T cells. Primed effector T cells are retained in the infected CNS if antigen is encountered in proper MHC context and may deliver signals that potentiate microglia to enhanced fungistasis. Vaccinated C57BL6/J mice resist an ordinarily lethal C. neoformans rechallenge, but identically treated congenic Abeta(o/o) mice (MHC class II-deficient; CD4(+) T-cell-deficient) do not. Nor can Abeta(o/o) mice be adoptively immunized by infusion of lymphocytes from vaccinated C57BL6/J donors, as are severe combined immunodeficient (SCID) mice (MHC class II-intact, lymphocyte-deficient). Chimeric (C57BL/6J:Abeta(o/o)) mice with class II expression likely on perivascular microglia only were, like SCID mice, capable of adoptive immunization against C. neoformans brain infection. To the contrary, chimeric mice with class II expression likely only on parenchymal microglia were not capable of effective adoptive immunization against C. neoformans brain infection. Therefore, in order to mediate resistance to infection, primed CD4(+) T cells must interact with the replenishable perivascular microglial subset that lies in close proximity to cerebral vasculature. Although T cells may supply help in the form of inflammatory cytokines to parenchymal microglia, expression of class II on these cells appears unnecessary for antifungal activity. (C) 2002 Wiley-Liss, Inc.