Comparative contribution of CD1 on the development of CD4⁺ and CD8⁺ T cell compartments

CD1 molecules are MHC class I-like glycoproteins whose expression is essential for the development of a unique subset of T cells, the NK T cells. To evaluate to what extent CD1 contributes to the development of CD4⁺ and CD8⁺ T cells, we generated CD1°II°and CD1°TAP°mice and compared the generation of T cells in these double-mutant mice and II°or TAP°mice. FACS analysis showed that the number of CD4⁺ T cells in CD1°II°mice was reduced significantly compared with the corresponding population in II°mice. Both CD4⁺ NK1.1⁺ and the CD4⁺ NK1.1^- population were reduced in CD1°II° mice, suggesting that CD1 can select not only CD4⁺ NK1.1⁺ T cells but also some NK1.1^- CD4⁺ T cells. Functional analysis showed that the residual CD4⁺ cells in CD1°II°can secrete large amounts of IFN-γ and a significant amount of IL-4 during primary stimulation with anti-CD3, suggesting that this population may be enriched for NK T cells restricted by other class I molecules. In contrast to the CD4⁺ population, no significant differences in the CD8⁺ T cell compartment can be detected between TAP°and CD1°TAP° mice in all lymphoid tissues tested, including intestinal intraepithelial lymphocytes. Our data suggest that, unlike other MHC class I molecules, CD1 does not contribute in a major way to the development of CD8⁺ T cells.