M cell-targeted ocular immunization: effect on immunoglobulins in tears, feces, and serum.
M cell-targeted ocular immunization: effect on immunoglobulins in tears, feces, and serum.
复制标题
M 细胞靶向眼部免疫：对眼泪、粪便和血清中免疫球蛋白的影响。
DOI：
10.1167/iovs.09-4491
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发表时间：
2010
影响因子：
4.4
通讯作者：
Liu,Hongshan
中科院分区：
文献类型：
--
作者：
Phillips,ThomasE;Sharp,Jeremy;Rodgers,Kay;Liu,Hongshan
目的：本研究探讨是否抗原采样M细胞，存在于滤泡相关上皮（FAE）以上组织结膜相关淋巴组织在兔，结合和逆向运输分泌型伊加（sIgA）的泪膜。对IgA介导的抗原摄取促进免疫球蛋白的局部和全身产生的假设进行了检验。通过免疫细胞化学表征了M细胞的sIgA结合和反向易位。在用山羊IgG抗兔伊加或非特异性山羊IgG局部和全身免疫后，使用酶联免疫测定法（ELISA）测量泪液、粪便和血清中的免疫球蛋白浓度。内源性sIgA与结膜M细胞顶膜结合。外源性抗IgA免疫球蛋白易位穿过M细胞。在免疫前动物的泪液中存在针对山羊IgG的显著水平的sIgA。局部应用山羊IgG特异性兔伊加或非特异性山羊IgG导致类似的增加，在抗原特异性伊加的眼泪，粪便和血清。泪液中的抗原特异性IgG反应反映了两种免疫原的血清反应，与该免疫球蛋白的渗出一致。泪液和血清中的IgM反应对两种免疫原都很弱。全身免疫不能维持或增强局部粘膜伊加应答。结膜M细胞结合并转运来自泪膜的sIgA。局部结膜免疫导致从局部和远处粘膜以及在血清中产生抗原特异性免疫球蛋白。免疫前泪膜中存在的天然抗体可能导致对山羊抗兔伊加和非特异性山羊IgG的类似免疫应答。
Purpose.: This study investigates whether antigen-sampling M cells, present in the follicle-associated epithelium (FAE) above organized conjunctiva-associated lymphoid tissue in rabbits, bind and retro-transport secretory IgA (sIgA) from the tear film. The hypothesis that IgA-mediated uptake of antigens promotes local and systemic production of immunoglobulins was tested.Methods.: sIgA binding and retro-translocation by M cells was characterized by immunocytochemistry. Immunoglobulin concentrations in tears, feces and serum were measured using enzyme-linked immunoassays (ELISA) after topical and systemic immunization with either goat IgG anti-rabbit IgA or nonspecific goat IgG.Results.: Endogenous sIgA was found associated with the apical membrane of conjunctival M cells. Exogenous anti-IgA immunoglobulins were translocated across M cells. Significant levels of sIgA against goat IgG were present in tears of pre-immune animals. Topical application of either goat IgG specific for rabbit IgA or nonspecific goat IgG led to similar increases in antigen-specific IgA in tear, feces, and serum. The antigen-specific IgG response in tears mirrored the serum response for both immunogens consistent with transudation of this immunoglobulin. The IgM response in tears and serum was weak for both immunogens. Systemic immunization did not sustain or enhance the local mucosal IgA responses.Conclusions.: Conjunctival M cells bind and translocate sIgA from the tear film. Topical conjunctival immunization leads to generation of antigen-specific immunoglobulins from both local and distant mucosae and in serum. Natural antibodies, present in the tear film before immunization, may have contributed to similar immune responses to goat anti-rabbit IgA and nonspecific goat IgG.