CD2 regulates the positive selection and function of antigen-specific CD4-CD8+ T cells

The CD2 glycoprotein has been implicated in both positive and negative regulation of T-cell mitogenesis. To study the involvement of CD2 in T-lymphocyte development and immune responses, we have analyzed two lines of CD2-null mice, each expressing a distinct class I major histocompatibility complex (MHC)-restricted T-cell receptor (TCR). In both situations, the absence of CD2 appeared to promote the positive selection of cells in a manner that is similar to that which occurs in the absence of CD5. Consistent with this, compound homozygotes that lacked both CD2 and CD5 showed evidence of enhanced positive selection even in the absence of a transgenic TCR. Despite the observed enhancement of positive selection, the lack of CD2 was associated with defects in proliferative responses and interferon-gamma production when transgenic thymocytes and mature T lymphocytes were stimulated with the appropriate antigens. These findings raise the possibility that impaired sensitivity to selecting ligands in the thymus may provide a selective advantage that improves the efficiency of positive selection for certain TCRs. Furthermore, the results highlight the potential for a differential role for CD2 in thymocyte selection and T-cell immune responses.