TCR-MHC class II interaction is required for peripheral expansion of CD4 cells in a T cell-deficient host

It is well established that T cell-deficient nude and SCID mice can be reconstituted by i.v. injection of small numbers of purified peripheral CD4(+) T cells; however, the requirements for expansion of the transferred T cells in such systems are not clear. We show here that blood and lymphoid organs of MHC class Il-deficient mice (which selectively lack mature CD4(+) T cells) cannot be reconstituted by transfer of purified splenic CD4(+) T cells, whereas TCR alpha-deficient mice (which lack both CD4(+) and CD8(+) mature T cells) are readily reconstituted. The failure of CD4(+) T cell reconstitution in MHC class Il-deficient mice was not due to the presence of CD8(+) T cells, since similar results were obtained in TCR alpha-MHC class II double-deficient mice. Consistent with most previous studies CD4(+) T cells in reconstituted TCR alpha-deficient mice had a diverse TCR V-beta repertoire and were predominantly of an activated/memory (CD44(high)) phenotype. Collectively our data demonstrate that the expansion of peripheral CD4(+) T cells in a T cell-deficient host is dependent upon interactions of the TCR with MHC class II.