MICE LACKING MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I AND CLASS-II MOLECULES

Mice lacking major histocompatibility complex (MHC) antigens were gene rated by mating beta2-microglobulin-deficient, and therefore class I-d eficient, animals with MHC class II-deficient animals. When housed und er sterile conditions, the resulting MHC-deficient mice appear healthy , survive for many months, and breed successfully. Phenotypically, MHC -deficient mice are depleted of CD4+ and CD8+ T cells in peripheral ly mphoid organs due to a lack of appropriate restricting elements. In co ntrast, the B-cell compartment of these animals appears intact, and MH C-deficient mice can mount specific antibody responses when challenged with a T-independent antigen. Spleen cells from MHC-deficient animals are poor stimulators and responders in a mixed lymphocyte reaction. D espite their relatively weak cellular immune responses in vitro, MHC-d eficient mice reject allogeneic skin grafts with little delay, and gra fts from MHC-deficient animals are rapidly rejected by normal allogene ic recipients. Taken together, these results emphasize the plasticity of the immune system and suggest that MHC-deficient mice may be useful for examining compensatory mechanisms in severely immunocompromised a nimals.