Immunoregulatory Functions for Murine htraepithelial Lymphocytes: 7/~ T Cell

Past work has shown that a subset of effector T cells with unique characteristics could abrogate haptenor 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 intraepitbelial 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 + 346 T cell receptor-positive (TCR+), but not ~//3 TCR + T cells, and "y/~ TCR + Tcs cells were associated with both the CD4-,CD8 + and CD4,CDS(double-negative) IEL fractions. The CD4-,CD8 + "y/6 TCR + IELs were further separated into Vicia villosa-adherent and -nonadherent fractions. Adoptive transfer of V. villosa-adherent "y/~ TCR + T cells to mice with OT to SRBC resulted in splenic IgA, IgM, and IgG subclass anti-SRBC responses, while V. villosa-nonadherent "y/tf TCR + T cells were without activity. The 3'/6 TCR + IELs did not support in vitro antibody responses in B cell cultures, while od3 TCR + IELs were effective T helper cells. Further, cytokine production by the 3//6 TCR + IELs was examined, and the 3'/6 TCR + V. villosa-adherent fraction, which possessed contrasuppressor function, contained low levels of I1:5 mRNA and small numbers of I1:5-producing cells when compared with oe/3 TCR + IELs and V. villosa-nonadherent "y/~ TCR + IELs. Our results now show that mouse IELs contain two distinct types of T cells that function in the immune response, e.g., or//3 TCR + T cells that produce I1:5 and function as helper cells, and 3'/6 TCR + T cells that restore antibody responses in mice that had been orally tolerized with antigen.