IMMUNITY TO ROTAVIRUS IN T-CELL DEFICIENT

Rotavirus infection was studied in adult nude mice (BALB/c background) , alpha beta or gamma delta and alpha beta/gamma delta T cell receptor (TCR) knockout (-/-) mice (C57BL/6 and C57BL/6x129 backgrounds), and SCID mice (C57BL/6 background). The gamma delta TCR -/- cleared infect ion just like control mice. All of the nude mice, alpha beta, alpha be ta/gamma delta 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 analysi s with spleen and lamina propia cells showed that the virus-specific i ntestinal IgA response in immunocompetent C57BL/6 mice was similar to the gamma delta TCR -/- mice and 7- to 60-fold higher than in the cup TCR -/- and alpha beta/gamma delta TCR -/- mice. Likewise, the respons e of nude +/- mice was 20 times greater than that of nude -/- litterma tes. While the intestinal IgA antibodies of C57BL/6 mice, gamma delta TCR -/- mice, and nude +/- mice recognized insect cells infected with recombinant baculovirus expressing rotavirus VP6 and VP4 proteins, tho se of the alpha beta TCR -/-, alpha beta/gamma delta TCR -/-, and nude -/- mice recognized only VP6. Immunocompetent C57BL/6 mice depleted o f CD4(+) T cell developed similar levels of rotavirus-specific intesti nal IgA as the alpha beta TCR -/- mice, suggesting that this T cell-in dependent IgA response is present in normal mice. in contrast to previ ously published results with BALB/c SCID and RAG 2 -/- (C57BL/6x129 ba ckground) mice, all of which become chronically infected with murine r otavirus, 40% of the C57BL/6 solo mice cleared primary rotavirus infec tion. These results suggest that both a T cell-independent antibody re sponse and innate mechanisms can contribute to immunity to murine rota virus and show that gamma delta T cells are not necessary for efficien t clearance of primary rotavirus infection in mice. (C) 1997 Academic Press.