Immunological studies of NK cell-deficient beige mice. II. Analysis of T-lymphocyte functions in beige mice.

Lymphocytes from natural killer (NK) cell-deficient beige mice have a poor ability to induce many different forms of graft-versus-host reaction (GvHR). In this study, we have examined whether this defect could reflect an associated abnormality in beige T-lymphocyte function. Compared with normal, congenic C57Bl/6 (B6) mice, beige mice had similar numbers and proportions of T-cell subsets and generated normal allospecific delayed-type hypersensitivity (DTH) responses in vivo. In addition, beige mice developed normal or enhanced DTH responses to the protein antigen, ovalbumin (OVA), and were fully susceptible to the induction of tolerance by feeding OVA. Beige lymphocytes recirculated normally in vivo and showed enhanced proliferative responses to mitogens and alloantigens in vitro. In contrast, beige responder cells generated poor cytotoxic T-lymphocyte (CTL) responses in vitro and had quantitatively identical defects in CTL and NK cell activation after alloimmunization in vivo. These results suggest that although many effector and regulatory T-cell functions are normal in beige mice, the NK-cell defect in these animals is paralleled by impaired CTL activity. We suggest that abnormal T-cell function accounts for the inability of beige lymphocytes to induce GvHR.