IMMUNOREGULATORY FUNCTIONS FOR MURINE INTRAEPITHELIAL LYMPHOCYTES - GAMMA-DELTA T-CELL RECEPTOR POSITIVE (TCR+) T-CELLS ABROGATE ORAL TOLERANCE, WHILE ALPHA-BETA-TCR+ T-CELLS PROVIDE B-CELL HELP

Past work has shown that a subset of effector T cells with unique characteristics could abrogate hapten- or antigen-induced tolerance, and the reconstitution of this immune response has been termed contrasuppression. We have studied contrasuppression in a model of oral tolerance (OT) in which adoptively transferred antigen-specific T contrasuppressor (Tcs) cells reverse OT and result in antibody responses to the eliciting antigen. In the present study, we show that murine intraepithelial lymphocytes (IELs) from mice orally immunized with sheep red blood cells (SRBC) contain T cells that exhibit Tcs cell activity. This effect was mediated by CD3+ gamma/delta T cell receptor-positive (TCR+), but not alpha/beta-TCR+ T cells, and gamma/delta TCR+ Tcs cells were associated with both the CD4-,CD8+ and CD4-,CD8- (double-negative) IEL fractions. The CD4-,CD8+ gamma/delta-TCR+ IELs were further separated into Vicia villosa-adherent and -nonadherent fractions. Adoptive transfer of V villosa-adherent gamma/delta-TCR+ T cells to mice with OT to SRBC resulted in splenic IgA, IgM, and IgG subclass anti-SR-BC responses, while V. villosa-nonadherent gamma/delta-TCR+ T cells were without activity. The gamma/delta-TCR+ IELs did not support in vitro antibody responses in B cell cultures, while alpha/beta-TCR+ IELs were effective T helper cells. Further, cytokine production by the gamma/delta-TCR+ IELs was examined, and the gamma/delta-TCR+ V villosa-adherent fraction, which possessed contrasuppressor function, contained low levels of IL-5 mRNA and small numbers of IL-5-producing cells when compared with alpha/beta-TCR+ IELs and V villosa-nonadherent gamma/delta-TCR+ IELs. Our results now show that mouse IELs contain two distinct types of T cells that function in the immune response, e.g., alpha/beta-TCR+ T cells that produce IL-5 and function as helper cells, and gamma/delta-TCR+ T cells that restore antibody responses in mice that had been orally tolerized with antigen.