In vivo role of lymphocyte subpopulations in the control of virus excretion and mucosal antibody responses of cattle infected with rotavirus

Abstract

T-cell control of primary rotavirus infection and mucosal antibody responses to rotavirus was studied with monoclonal antibodies (MAb) to deplete gnotobiotic calves of CD4+, CD8+, BoWC1+, or both CD4+ and CD8+ lymphocytes prior to infection with rotavirus. Injection of these MAb produced specific reductions in circulating and tissue lymphocyte subpopulations. Following infection, control calves developed fecal immunoglobulin M (IgM) and IgA antibodies and serum IgM and IgG1 antibodies; there was no IgG2 antibody produced. Anti-CD4-treated calves had reduced fecal and serum antibody responses to rotavirus compared with control calves. The IgM response was less affected than the other isotypes. Calves concurrently injected with MAb to CD4 and CD8 had antibody responses similar to those of calves injected with anti-CD4 antibody alone. No effect on serum or fecal antibody levels was seen when MAb to CD8 or BoWC1 were injected alone. Virus excretion was significantly increased in calves depleted of CD8+ cells. Depletion of CD4+ cells or BoWC1+ cells had no effect on virus excretion. Calves depleted of both CD4+ and CD8+ cells excreted amounts of virus similar to those of calves depleted of CD8+ cells alone. Onset and duration of virus excretion were not affected by any of the MAb treatments. We conclude that a CD8+ cell population is involved in limiting primary rotavirus infection, while CD4+ or BoWC1+ (gamma/delta+ TcR) lymphocytes are not. Furthermore, CD4+ lymphocytes (but not CD8+ or BoWC1+ lymphocytes) were shown to be important in the generation of mucosal, as well as systemic, antibody responses.