Immunity to Rotavirus in T Cell Deficient Mice

Abstract

Rotavirus infection was studied in adult nude mice (BALB/c background), αβ or γδ and αβ/γδ T cell receptor (TCR) knockout (−/−) mice (C57BL/6 and C57BL/6×129 backgrounds), and SCID mice (C57BL/6 background). The γδ TCR −/− mice cleared infection just like control mice. All of the nude mice, αβ, and αβ/γδ TCR −/− mice cleared primary rotavirus infection, with a short delay, compared to immunocompetent control mice and developed a rotavirus-specific intestinal IgA measured by ELISA. Elispot analysis with spleen and lamina propia cells showed that the virus-specific intestinal IgA response in immunocompetent C57BL/6 mice was similar to the γδ TCR −/− mice and 7- to 60-fold higher than in the αβ TCR −/− and αβ/γδ TCR −/− mice. Likewise, the response of nude +/− mice was 20 times greater than that of nude −/− littermates. While the intestinal IgA antibodies of C57BL/6 mice, γδ TCR −/− mice, and nude +/− mice recognized insect cells infected with recombinant baculovirus expressing rotavirus VP6 and VP4 proteins, those of the αβ TCR −/−, αβ/γδ TCR −/−, and nude −/− mice recognized only VP6. Immunocompetent C57BL/6 mice depleted of CD4+T cell developed similar levels of rotavirus-specific intestinal IgA as the αβ TCR −/− mice, suggesting that this T cell-independent IgA response is present in normal mice. In contrast to previously published results with BALB/c SCID and RAG 2 −/− (C57BL/6×129 background) mice, all of which become chronically infected with murine rotavirus, 40% of the C57BL/6 SCID mice cleared primary rotavirus infection. These results suggest that both a T cell-independent antibody response and innate mechanisms can contribute to immunity to murine rotavirus and show that γδ T cells are not necessary for efficient clearance of primary rotavirus infection in mice.