Infections of the intestinal tract are among the most prevalent causes of disease and death worldwide. In Asia, Africa and Latin America, between 1978 and 1979, 3 to 5 billing cases of diarrhea accounted for 5 to 10 million deaths. The devastating impact of these pathogens has excited interest in host immunity at the intestinal mucosal surface. Much of this interest has focused on the importance of secretory IgA. However, the role of intestinal T lymphocytes in intestinal infections has not been explored. Considering that a sizable portion of the host's total number of T cells is contained in gut-associated lymphoid tissue or GALT (composed of intraepithelial, lamina propria and peyer's patch compartments), little is known about the function of these cells in protection against enteric disease. We will examine the importance of GALT cytotoxic T lymphocytes (CTLs) in protection against gastroenteritis. Infection of adult and suckling mice with a common intestinal pathogen, rotavirus, will be used to determine 1) the kinetics of rotavirus-specific intenstinal and non-intestinal CTLs after intestinal infection, 2) the requirement for viral replication in the intestinal in eliciting CLTs, 3) the importance of CTLs in protection against rotavirus gastroenteritis, and 4) the rotavirus antigens recognized by serotype-specific and cross-reactive CTLs. We recently found that mice orally inoculated with rotaviruses develop a primary, rotavirus-specific CLT response. Rotaviruses are an excellent pathogen for the study of intestinal immunity. These viruses are ubiquitous in nature and infect the young of many mammalian and avian species. In addition, rotaviruses are the most common causes of infant and childhood gastroenteritis both in the United States and in developing countries. The worldwide impact of rotavirus-induced diarrhea has excited interest in disease prevention by the development of a vaccine. Recently, murine rotaviruses have been adapted to growth in tissue culture. Tissue culture-adapation allows for an accurate determination of the viral dose used for in vitro and in vivo infections. Unlike other viruses used to study CLTs in experimental animals, murine rotaviruses are a virulent, natural host pathogen. The pattern of viral replication, diarrhea, and spread found in mice after oral inoculation with these viruses mimics that found in human disease. Thus, the rotavirus-specific CTL response in mice should mimic the human response.
