Date of Award

1993

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Edgar Don Roberts

Abstract

Five Macaca mulatta were infected with SIV/DELTA$\sb{\rm B670}.$ Approximately 70 days later, this group (SIV) and five age, sex, weight matched not SIV-infected (NEG) M. mulatta were inoculated orally with approximately $3\times10\sp{10}$ Campylobacter jejuni. Small and large bowel mucosal biopsies, bowel contents, sera, blood, and rectal swabs were collected before and after C. jejuni inoculation. Biopsy cryosections were stained with histologic stains and immunocytochemically for lymphocyte subsets, plasmacytes, macrophages, and B-cells. Coded stained sections were examined semiquantitatively or quantitatively using computerized image analysis. Circulating lymphocyte subsets were determined using FACS analysis. Campylobacter jejuni was recultured from 4/5 SIV and 4/5 NEG monkeys on PI-day three, 3/5 SIV monkeys on PI-day seven, and 1/5 SIV monkeys on PI-day 28. No clinical signs were observed. Very rare, mildly dilated crypts lined by flattened epithelium were observed in mucosal biopsies of one SIV and one NEG monkey. As in AIDS, the SIV group had significantly (p $<$ 0.05) increased numbers of mucosal CD8+ and IgM+ cells. There were fewer, but not significantly reduced numbers of IgA+ cells in the colonic mucosa. CD4+ cells, decreased in AIDS, were not significantly different between SIV and NEG groups. Circulating CD4+CD29+ cells were significantly decreased while circulating lymphocytes and CD4+ cells approached significant reduction. Following C. jejuni inoculation, systemic anti-C. jejuni IgA and IgG responses determined by ELISA had similar patterns. For SIV monkeys, 4/5 had no or minimal increases in titers while 4/5 NEG monkeys had moderate to marked relative increases. The trend of most of the colonic but not duodenal contents responses roughly paralleled the systemic IgA response. Comparing measured cell populations or ratios with antibody responses suggested correlations but no cell population consistently predicted the level of antibody responses in individual monkeys. These studies found that the SIV-infected macaque model has mucosal immune system morphologic alterations similar to AIDS patients. The alterations are associated with a reduced specific antibody response to and prolonged colonization by C. jejuni but without increased virulence. Further studies defining and using this model are warranted.

Pages

141

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