Schneider T, Ullrich R, Zeitz M
Medical Clinic II, University of the Saarland, Homburg/Saar, Berlin, Germany.
Semin Gastrointest Dis. 1996 Jan;7(1):19-29.
The intestinal (in particular rectal) mucosa is an important portal of entry of human immunodeficiency virus (HIV) in homosexual men, who represent the vast majority of HIV-infected patients in Europe and North America. There are several possibilities for HIV to reach the CD4+ T cells, macrophages, and follicular dendritic cells in the intestinal mucosa. HIV may be transported through M cells directly to mucosal lymphoid follicles. Alternatively, HIV may infect enterocytes via Fc-receptor by antibody-bound HIV or via a CD4 independent receptor. By successive budding on the basal side of enterocytes, HIV may be released into the lamina propria. Furthermore, in patients not infected by the intestinal route, HIV may also rapidly enter the intestinal mucosa by other mechanisms: intestinal T-lymphocytes are mainly activated memory T cells reentering the mucosal surfaces after circulating through the peripheral blood. In the periphery they may have been preferentially infected by HIV. Accumulation of infected T cells could thus occur in the intestinal mucosa. The special phenotypical and functional characteristics of intestinal T lymphocytes may affect the replication and cytopathicity of HIV, resulting in an accelerated loss of CD4 positive T cells in the lamina propria. CD4 T cells play a critical role in antigen-dependent B cell differentiation, thus the pronounced CD4 T cell depletion in the intestinal mucosa may be responsible for the observed decrease of IgA plasma cells and a reduced secretion of IgA2. Depletion and functional impairment of activated mucosal lamina propria lymphocytes by HIV infection could explain the break-down of the mucosal immune barrier leading to secondary opportunistic or nonopportunistic infections and secondary malignancies. In addition, because of the interrelation between the mucosal immune system and the epithelium these changes might be responsible for the partial small intestinal mucosal atrophy and maturational defects in enterocytes observed in HIV-infected patients. To be effective, a future prophylactic vaccine against HIV has to be able to induce not only systemic but also a local mucosal cellular and humoral protective immune response.
肠道（尤其是直肠）黏膜是人类免疫缺陷病毒（HIV）进入同性恋男性体内的重要途径，在欧洲和北美，同性恋男性占绝大多数HIV感染患者。HIV有多种途径可接触到肠道黏膜中的CD4+T细胞、巨噬细胞和滤泡树突状细胞。HIV可通过M细胞直接转运至黏膜淋巴滤泡。或者，HIV可通过抗体结合的HIV经Fc受体或通过CD4非依赖性受体感染肠上皮细胞。通过在肠上皮细胞基底侧连续出芽，HIV可释放至固有层。此外，在非经肠道途径感染的患者中，HIV也可通过其他机制迅速进入肠道黏膜：肠道T淋巴细胞主要是循环至外周血后重新进入黏膜表面的活化记忆T细胞。在周围组织中，它们可能已被HIV优先感染。因此，感染的T细胞可能在肠道黏膜中积聚。肠道T淋巴细胞特殊的表型和功能特性可能影响HIV的复制和细胞病变效应，导致固有层中CD4阳性T细胞加速丢失。CD4 T细胞在抗原依赖性B细胞分化中起关键作用，因此肠道黏膜中明显的CD4 T细胞耗竭可能是观察到的IgA浆细胞减少和IgA2分泌减少的原因。HIV感染导致活化的黏膜固有层淋巴细胞耗竭和功能受损，这可以解释黏膜免疫屏障的破坏，从而导致继发性机会性或非机会性感染以及继发性恶性肿瘤。此外，由于黏膜免疫系统与上皮细胞之间的相互关系，这些变化可能是HIV感染患者中观察到的部分小肠黏膜萎缩和肠上皮细胞成熟缺陷的原因。为了有效，未来针对HIV的预防性疫苗不仅必须能够诱导全身免疫反应，还必须能够诱导局部黏膜细胞免疫和体液免疫保护反应。
