Association between the degree of thymic dysplasia and the kinetics of thymic NK cell activity during the graft-versus-host reaction

Abstract

In this study, by employing different cell doses and parent into F 1 hybrid combinations, we have investigated the relationship between the severity of thymic medullary dysplasia and the kinetics of thymic natural killer (NK) cell activity after the induction of graft-versus-host (GVH) reactions. GVH reactions were induced by injecting different doses (30, 20, 10 × 10 6) of C57BL 6 (B6) of A parental lymphoid cells (PLC) into non-X-irradiated adult B6xAF 1 (B6AF 1) mice. On different days after the induction of GVH reactions, the thymuses were examined histologically and thymocyte NK cell activity was tested by using YAC targets. Our results show that, depending upon the genotype and dose of PLC injected, various degrees of thymic medullary dysplasia (mild, moderate, or severe) can be induced. Furthermore, severe to moderate thymic medullary dysplasia is observed only in those groups of GVH-reactive mice in which thymic NK cell activity occurs early and increases rapidly. In contrast, when mild thymic medullary dysplasia or no thymic alterations was observed, thymic NK cell activity peaked later and was of lower intensity than that of the groups with moderate to severe lesions. These results suggest an association between the degree of thymic medullary dysplasia and the kinetics of NK cell activity in the thymus. Furthermore, the different degrees of thymic medullary dysplasia as described here may serve as a powerful tool to study the role of thymic medullary dysplasia in determining the duration of T-cell immunodeficiency associated with the GVH reactions.