Negative regulation of CD4 lineage development and responses by CD5

CD5 deficiency results in a hyper-responsive phenotype to Ag receptor stimu lation. Here we show that the development and responses of CD4 lineage T ce lls are regulated by the function of CD5, Thymocytes expressing the I-A(d)- restricted D011.10 TCR undergo abnormal selection without CD5. In H-2(d) mi ce, the absence of CD5 causes deletion of double-positive thymocytes, but a llows for efficient selection of cells expressing high levels of the D011.1 0 clonotype, By contrast, there is enhanced negative selection against the D011.10 clonotype in the presence of I-A(b), T cell hybridomas and D011.10 T cells are more responsive to TCR stimulation in the absence of CD5, Such hypersensitivity can be eliminated by expression of wild-type CD5, but not by a form of CD5 that lacks the cytoplasmic tail. Finally, CD5 deficiency p artially suppresses the block of CD4 lineage development in CD4-deficient m ice. Taken together, the data support a general role for CD5 as a negative regulator of Ag receptor signaling in the development and immune responses of CD4 lineage T cells.