HD MICE - A NOVEL MOUSE MUTANT WITH A SPECIFIC DEFECT IN THE GENERATION OF CD4(-CELLS() T)

We have identified a spontaneous mutation in mice, which we term HD fo r ''helper T cell deficient.'' This mouse is distinguished by the virt ual absence of peripheral T cells of the CD4(+)8(-) major histocompati bility complex (MHC) class II-restricted T helper subset due to a spec ific block in thymic development, The developmental defect is selectiv e for CD4+8- cells; the maturation of CD4(-)8(+) and gamma delta T cel ls is normal. The autosomal recessive mutation underlying the HD pheno type is unrelated to MHC class II, since it segregates independently o f the MHC class II locus. Moreover, the HD phenotype is not caused by a defect of the CD4 gene. Bone marrow transfer experiments demonstrate that the defect is intrinsic to cells of the hematopoietic lineage, i .e., most likely to developing thymocytes themselves. The frequency of CD4(+)8(low) intermediate cells is markedly increased in HD mice, sug gesting that class II-restricted thymocytes are arrested at this stage , This is the first genetic defect of its kind to be described in the mouse and may prove highly informative in understanding the molecular pathways underlying lineage commitment.