Cytotoxic T cells in AIDS colonic cryptosporidiosis

Abstract

Background/Aims-It is not known how enteric cryptosporidiosis induces severe intestinal impairment despite minimal invasion by the parasite. The aim of this study was to analyse the histological features and locally implicated immune cells in colonic biopsies of AIDS related cryptosporidiosis. Patients/Methods-Colonic biopsies from patients with AIDS related cryptosporidiosis (n = 10, group I), patients with AIDS but without intestinal infection (n = 9, group II), and human seronegative controls (n = 9, group III) were studied. Using immunohistochemistry the infiltrating mononuclear cells were analysed in both the epithelium and lamina propria for the expression of CD3, CD8, TiA1, granzyme B, and CD68 and for glandular expression of human major histocompatibility complex DR antigen (HLA-DR). Results-Severe histological changes, resulting in abundant crypt epithelial apoptosis and inflammatory infiltrate in the lamina propria, were seen in all biopsies from group I. A significant increase of CD8+, TiA1+, and granzyme B+ T cells in the lamina propria and HLA-DR glandular expression was noted in group I compared with groups II and III. However, the number of intraepithelial lymphocytes, lamina propria CD3+ T cells, and macrophages was not significantly increased in cryptosporidiosis specimens compared with controls. Conclusion-Epithelial apoptosis mediated by granzyme B+ cytotoxic host T cells might play a major role in the development of colonic lesions in AIDS related cryptosporidiosis. (J Clin Pathol 2001;54:298-303)

An Early Intestinal Mucosal Source of Gamma Interferon Is Associated with Resistance to and Control ofCryptosporidium parvumInfection in Mice

“…Increased numbers of small intestinal iIEL, particularly CD8 ϩ cells, and lamina propria lymphocytes have been reported as early as 3 days after C. parvum infection in several different mammalian species (1,2,6,8,11,12,20,28,29). More definitively, other studies have used adoptive transfer to show that iIEL promote the resolution of infection in chronically infected scid mice (22). In contrast to what is known for animals, our understanding of the mucosal immune response in human cryptosporidiosis is more limited.…”

Chronic intestinal graft-versus-host disease: clinical, histological and immunohistochemical analysis of 17 children

“…The apoptotic process is probably mediated by the cytotoxic T lymphocytes CD3 + , CD8 + , TiA1 + which are significantly increased in lamina propria in the case of chronic GVHD and acute GVHD. 31,41 In contrast, granzyme B expression was not increased in the case of acute and chronic GVHD. This result is in agreement with previous work showing no perforin expression in chronic GVHD skin biopsies but keratinocyte membrane expression of Fas.…”

“…Indeed, in our experience of cryptosporidiosis without GVHD there is an increase of granzyme B expression in lamina propria, but not when cryptosporidiosis was associated with GVHD. 31 Epithelial cell apoptosis can also be induced in AIDS [32][33][34] or in constitutional immunodeficiency, 35 inflammatory bowel disease, 36 drug-related lesions, 37 melanosis coli, 38 radiation colitis 38 and infectious colitis. 39 Epithelial cell apoptosis in enteric biopsy after BMT is abnormal, 32 suggesting a pathologic process, but is not specific to GVHD.…”

Increased inherent intestinal granzyme B expression may be associated with SIV pathogenesis in Asian non-human primates

“…Two studies in HIV + humans reported increased GrB expression in the duodenal and colonic LP respectively [23, 28]. The first study found that 22 of the 29 patients with HIV + had between 5 and 10 GrB + cells per high‐powered field (HPF) in the duodenal LP.…”

“…Similarly, another laboratory found that the percentage of GrB + cells in the colonic LP was significantly higher in patients with AIDS compared to healthy controls (2.2% and 0.2% respectively). When colon samples from patients with AIDS co‐infected with Cryptosporidiosis were examined, the proportion of GrB + cells increased to 8.7% [23]. These findings suggest that interaction of LP lymphocytes with microbial products may amplify the release of GrB in a positive feedback loop whereby microbial translocation results in more GrB release that further damages the epithelium, thus allowing even more microbial translocation.…”