DEVELOPMENT OF MUCOSAL AND SYSTEMIC LYMPHOPROLIFERATIVE RESPONSES ANDPROTECTIVE IMMUNITY TO HUMAN GROUP-A ROTAVIRUSES IN A GNOTOBIOTIC PIGMODE

Gnotobiotic pigs were orally inoculated with virulent Wa strain (G1P1A [8]) human rotavirus (group 1), attenuated Wa rotavirus (group 2) or d iluent (controls) and were challenged with virulent Wa rotavirus 21 da ys later. On various postinoculation or postchallenge days, virus-spec ific responses of systemic (blood and spleen) and intestinal (mesenter ic lymph node and ileal lamina propria) mononuclear cells (MNC) were a ssessed by lymphoproliferative assays (LPA). After inoculation, 100% o f group 1 pigs and 6% of group 2 pigs shed virus. Diarrhea occurred in 95, 12, and 13% of group 1, group 2, and control pigs, respectively. Only groups 1 and 2 developed virus-specific LPA responses prior to ch allenge. Group 1 developed significantly greater mean virus-specific L PA responses prior to challenge and showed no significant changes in t issue mean LPA responses postchallenge, and 100% were protected agains t virulent virus challenge. By comparison, both group 2 and controls h ad significantly lower LPA responses at challenge and both groups show ed significant increases in mean LPA responses postchallenge. Eighty-o ne percent of group 2 and 100% of control pigs shed challenge virus, a nd both groups developed diarrhea that was similar in severity postcha llenge. The virus-specific LPA responses of blood MNC mirrored those o f intestinal MNC, albeit at a reduced level and only at early times po stinoculation or postchallenge in all pigs. In a separate study evalua ting antibody-secreting-cell responses of these pigs (L. Yuan, L. A. W ard, B. I. Rosen, T. L. To, and L. J. Saif. J. Virol. 70:3075-3083, 19 96), we found that the magnitude of a tissue's LPA response positively correlated with the numbers of virus-specific antibody-secreting cell s for that tissue, supporting the hypothesis that the LPA assesses T-h elper-cell function. The magnitude of LPA responses in systemic and in testinal tissues also strongly correlated with the degree of protectiv e immunity elicited by the inoculum (p = 0.81). We conclude that blood may provide a temporary ''window'' for monitoring intestinal T cells and that the LPA can be used to assess protective immunity to human ro taviruses.