The intestinal mucosa is depleted of CD4+ T cells very early after intravenous inoculation with SIV, and this occurs long before CD4 T cell depletion is detected in blood, lymph nodes, or spleen. of SIV-infected rectal mucosa contained increased numbers of IgM+ cells, confirming earlier observations in small intestine and colon. The data suggest that antigen-presentation capacity is definitely taken care of in inductive sites of SIV-infected rectal mucosa, but immune effector functions may be modified. The mucosa of the gastrointestinal (GI) tract is definitely rich in cells of the immune system including triggered T cells, macrophages, and dendritic cells which are focuses on of human being immunodeficiency computer virus (HIV) and simian intestinal computer virus (SIV). Indeed, the GI mucosa is definitely actively involved in HIV/SIV illness; 1,2 viral presence has been recorded in the mucosa of the small intestine and colon of HIV-infected individuals 3,4 and SIV-infected macaques. 5-7 The prevalence of opportunistic intestinal infections in HIV/SIV-infected individuals 8,9 could be because of impairment of mucosal immune responses or to other effects of local viral replication in the intestinal mucosa. The intestinal mucosa is definitely depleted of CD4+ T cells Schizandrin A very early after intravenous inoculation with SIV, and this occurs long before CD4 T cell depletion is definitely detected in blood, lymph nodes, or spleen. 10,11 These results, which have been individually confirmed, 12,13 entailed quantitation of cells in the duodenum, jejunum, and colon but did not include the rectal mucosa. The rectal mucosa is definitely of particular importance in HIV/SIV illness and transmission for a number of reasons. It is rich in lymphoid aggregates and follicles which have been shown to be sites of viral replication in HIV-infected individuals. 4 Viral production in the rectal mucosa has been implicated in transmission of HIV from infected hosts to uninfected individuals. 14 The rectal mucosa gives a relatively easy site for sampling of the GI mucosa in humans. In addition, the rectal mucosa is definitely a site of initial HIV/SIV access. 7,15,16 Administration of antigens via the rectum of humans results in local and systemic immune reactions, 17,18 making the rectal mucosa an important candidate route for delivery of HIV/SIV vaccines. The cell populations responsible for induction of local immune reactions in the structured lymphoid cells of the small intestine (ie, the Peyers patches) have been studied in some fine detail, 19,20 but much less is known about the lymphoid cells of the rectum. We consequently undertook an Schizandrin A immunocytochemical study of the rectal mucosa in normal and SIV-infected rhesus macaques to investigate possible alterations in the cellpopulations responsible for mucosal immune function. In the intestinal mucosa, the inductive and effector arms of the immune system are anatomically unique. Inductive sites consist of organized lymphoid cells, seen in the rectum as isolated rectal lymphoid nodules (RLN), whereas effector sites are displayed by lymphocytes spread diffusely throughout the lamina propria (LP) and within the epithelium. In this study, the RLN and LP were examined separately, because the cellular compositions of the two compartments are unique and thus the effects of SIV illness may differ. For example, in the rectal mucosa of HIV-infected humans, depletion of CD4+ lymphocytes is definitely more severe in the LP than in the RLN. 21 HIV/SIV illness could nevertheless interfere with the induction of immune reactions in the RLN by influencing the control and demonstration of incoming foreign antigens and pathogens, depleting T cell help for generation of antigen-specific B cells and cytotoxic T lymphocytes (CTLs), and impairing cytokine production for isotype switch to IgA. In the LP, illness could disrupt additional mucosal protective functions. Indeed, others have observed modified morphology of subepithelial macrophages in SIV-infected monkey colon 5,6 and a reduction in LP IgA-producing cells in both HIV-infected humans and SIV-infected macaques. 21-23 To examine in more detail the effects of SIV illness on both inductive and effector sites Rabbit Polyclonal to TF2H2 in the rectal mucosa, cells with antigen-presentation capacity in both RLN and LP were recognized by visualizing MHC-II and the co-stimulatory molecules CD40 and B7-2 (CD86). Possible alterations in mucosal homing/trafficking of cells to both compartments were evaluated by immunocytochemical recognition of cells expressing the mucosal homing receptor 47 and the peripheral lymph node homing receptor L-selectin. In addition, possible alterations in B cell populations were analyzed with regard to manifestation of molecules associated with antigen demonstration (MHC-II and CD40), differentiation state (CD20), and manifestation of immunoglobulin isotypes. Materials and Methods Animals Rectal and distal colonic cells (defined here Schizandrin A as 3 to 10 cm and 10 to 15 cm from your anal verge,.