Intestinal coccidiosis: using targeted mutagenesis to examine the role of αβ and γδ T-cells in the primary and secondary host response to Eimeria

The crypt epithelial cells of the routine small intestine are targets for infection by Emeria vermiformis. Other species of this genus of protozoan parasites target many vertebrates including birds and reptiles. In fact, Eimeria infection of poultry is of considerable commercial importance. Eimeria infection induces crypt hyperplasia, munosal inflammation, and villous atrophy. However, the mechanism by which animals become immune to Eimeria is poorly understood. To approach this issue, we have studied the immune response to Eimeria in immunocompetent mice, and in mice rendered deficient in cO o r ~ T-cells or B cells by targeted gene disruption. The duration and severity of infection was monitored by counting the number of infectious oocysts shed in the feces. We can conclude from our studies that infection elicits increases in both the cO and "~ T-cell repertoires in the local lymph nodes, and within the epithelium itself. However, attenuation of primary infection and the development of parasite-specific immunity are dependent entirely on cO T cells, und not on either ~ T-cells or B-cells. We are currently studying the contribution of ~6 T-cells to the regulation of epithelial celi turnover and the control of inflammation during the infection. Recent data will be presented. • EFFECT OF PLA2 INHIBITORS UPON THE INFLAMMATORY RESPONSE IN AN IN VIVO MODEL OF NECROTIZING ENTEROCOLITIS. JK Roche. L VanHoru, RL Guerrant. Department of Internal Medicine, University o f Virginia Health Sciences Center, Charlottesville, VA. Neerotizing enterocolitis (NEe) is the most serious gastroenterological disorder affecting premature infants. It is characterized by segmental bowel inflammation and sometimes perforation, biliary pneumatosis, and failure to gain weight. We chose to study how local mucosal substances might modify pathophysiological mechanisms responsible for the intestinal lesions, through pharmacological blocking of requisite pro-inflammatory mediators. The model system, adapted from that of Clark et a/. (Ped. Res. 19:919), used ligated rat intestinal segments exposed to acidified casein injected intraluminslly (small bowel and colon), where inflammatory lesions are quantitated as an enhanced volume/length (V/L) ratio (indicating a secretory response) as Well as by macroscopic appearance and histology of the intestinal mucosa. Quinacrine was found to reduce the inflammatory secretion by > 50%, when injected intraluminally with the inciting agent (acidified casein) (Fig. 1). This result was found in both colon and small bowel, at several points after lesion induction (3 and 6 hours), and did not rely on systemic absorption of the quinecrine, e.g., lesions developed in intestinal loops adjacent to ,o