Delayed-type hypersensitivity (DTH) reaction to rotavirus EDIM and RRV. Part 3
Sheridan et al. was one of the first to describe a mouse model studying rotavirus-specific immunity. Mice (CD-1) were infected orally with EDIM virus at 1, 7 or 21 days of age. Severe disease was observed in animals infected at 1 day of age and lasted for at least 9 days. Disease was observed in mice infected at day 7 of age also, but was less severe and lasted only 5 days. Mice infected at 21 days of age did not show any evidence of clinical illness. These findings were comparable to our study where the mice were inoculated with RRV at day 7 of age and illness and diarrhea was seen for 5 days in approximately 70% of the animals. If the animals were supplemented with rotavirus-specific antibodies (Gastrogard-R®) orally, the animals were protected completely from rotavirus-induced diarrhea. Inoculation of EDIM at day 17 of age did not result in any clinical symptoms and infection was measured by the analysis of rotavirus shedding in feces. Fecal viral shedding after a secondary EDIM inoculation showed that a primary rotavirus infection protected against viral shedding by 81% during a secondary inoculation. Administration of Gastrogard-R®, which completely protected the mice from diarrhea and illness during a primary infection, showed no protection during the secondary inoculation though the viral shedding seemed to disappear more rapidly compared to the group which received only EDIM without primary RRV inoculation.
Delayed-type hypersensitivity (DTH) is an important in vivo manifestation of cell-mediated immune responses. In our study, a rotavirus-specific DTH using EDIM was elicited at day 27 of age. In mice only inoculated with RRV at day 7, no DTH response was measurable compared to the control group. The mice receiving only EDIM at the age of 17 days however showed a significant DTH response to EDIM. This DTH disappeared in the mice which have been inoculated with both RRV and EDIM. Thus, not only adult mice that were re-infected after a primary infection showed a suppressed DTH as seen previously by Sheridan et al but also mice who received the primary infection at a young age and a re-infection at an older age showed the same DTH suppression. Cellular responses to rotavirus were also analyzed by ex vivo restimulation of T cells isolated from the spleen with UV-inactivated rotavirus. Inactivation by exposure to UV radiation destroys the integrity of rotavirus RNA and also removes the non-specific stimulatory effects of the virus when assayed on non-immune cells. A disadvantage of UV-inactivation over live virus is that inactivated virus has been shown to produce a lower level of proliferation than that induced by live virus. In the present experiments, the proliferation level was low, although a significant increase in T cell proliferation was seen in the mice receiving both RRV and EDIM and also in the Gastrogard-R® group. In these mice, even though during a primary infection clinical illness was completely blocked, the immune system was activated.