AEGiS-11IAC: Immunological study of the macaque digestive mucosa before and after rectal SIV infection.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Immunological study of the macaque digestive mucosa before and after rectal SIV infection.

Int Conf AIDS 1996 Jul 7-12; 11:14 (abstract no. We.A.395)
Couedel-Courteille A, Butor C, Guillet JG, Venet A; INSERM, ICGM, Paris, France.

OBJECTIVES: In order to study the evolution of the different parameters of the early cellular mucosal immune response in SIV rectally-infected macaques, we have first analysed the digestive mucosal immune system of healthy uninfected macaques.

METHODS: Healthy and SIV rectally-infected macaques (pathogenic isolate SIVmac 251) were sacrified (at day 7 and 14 post-infection). Standard and ultrastructural histologic examination was performed. Phenotypical analysis was done on purified lymphocyte suspensions and by immunohistochemistry. Functional studies were performed on purified cell suspensions obtained after epithelial and lamina propria (LP) enzymatic dilaceration. Several parts of digestive mucosa were examined (small, large intestine and rectum).

RESULTS: We first showed that macaque mucosa is strikingly similar to that of humans. Histological and ultrastructural studies showed morphological patterns comparable to human mucosa including the presence and distribution of epithelial cell membrane antigens (galactosylceramide, carcinoembryonic antigen, blood group H antigen). Phenotypic analysis, realised on intraepithelial lymphocytes (IEL) and lymphocytes of the LP (LPL) show high proportion of CD2+ T cells and low numbers of CD20+ B cells. The majority of T cells express the CD8 marker, particularly in the IEL fraction (80%). No major difference was observed between small intestine and rectum mucosa. About 80% of IEL and 40% of LPL present the characteristic marker of mucosal lymphocytes, CD103 (alphaEbeta7) revealed by HML-1 antibody. Functional studies (proliferation and cytotoxicity) show results similar to those described in humans. In a second part, macaques were rectally infected with SIV. Preliminary results show no main changes after infection as compared to healthy macaques in terms of histologic, phenotypic and functional studies. Viral load is however greater in local mucosal than in peripheral lymph nodes. SIV-specific immune responses are preferentially found in draining mesenteric lymph nodes at early time-points.

CONCLUSIONS: The remarkable similarity of human and macaque digestive mucosa, specially on an immunological viewpoint, strengthens the validity of the macaque model to study mucosal immune response to HIV/SIV infection.

Keywords: AEGIS, SIV, Macaca, Mucous Membrane, Rectum, Immunity, Mucosal, CD8-Positive T-Lymphocytes, CD4-Positive T-Lymphocytes, Lymphoid Tissue, Lymph Nodes, B-Lymphocytes, Immunization, Galactosylceramides, HIV, T-Lymphocytes, Animal, Human, immunology, complications, ICA11

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WeA395