Immune Responsiveness of Lymphotoxin-α-Deficient Mice: Two Reconstitution Models

The effects of lymphotoxin-α (LT-α) deficiency on mucosal immune status has not been defined. We utilized severe combined immunodeficiency (scid) mice as recipients of both mutant and wild-type whole splenocytes to determine whether lymphocytes from mutant mice had impaired homing ability. We also utilized irradiated mutant mice as recipients of wild-type whole splenocytes to determine whether lymphoid tissue anlages had, indeed, failed to develop as a consequence of LT-α deficiency. Subsequently, all mice were immunized orally with an attenuated strain ofSalmonella typhimuriumand mucosal IgA responses were monitored. The data presented here demonstrate thatscidrecipients generate mucosal responses equally well when reconstituted with mutant or wild-type lymphocytes. In contrast, reconstitution of mutant mice with wild-type cells failed to affect the efficiency of their mucosal immunity. The mutant phenotype, therefore, appears to involve neither impaired lymphocyte homing nor function in the generation of mucosal immunity. However, the mutant phenotype and immune responsiveness cannot be transformed merely by the provision of LT-α-expressing donor cell populations. The consequence of LT-α deficiency on mucosal immune responsiveness appears to be due to the lack of gut-associated lymphoid tissues, which may include the spleen, in mutant mice.