Subpopulations of CD4⁺ cells in lpr/lpr mice: differences in expression of T cell receptor/CD3 complex and proliferative responses

CD4⁺ cells from autoimmune-prone C57BL/6 lpr/lpr mice contain two subpopulations, B220^-CD4⁺ and B220⁺CD4⁺ cells. Highly purified B220^-CD4⁺ cells from C57BL/6 +/+ and lpr/lpr mice were examined by comparing functional characteristics and expression of cell surface antigens and T cell receptor (TcR)/CD3 complex. Both lpr B220⁺CD4⁺ and B220⁺CD4^-CD8^- cells, most of which were PgP-1 positive, expressed TcR/CD3 complex on the cell surface at lower level as compared with B220^-CD4⁺ cells of age-matched normal mice. In addition, the B220^-CD4⁺ cells were heterogeneous on the basis of surface expression of PgP-1 and CD3 antigens. Normal levels of TcR C(α)-, C(β)- and V(β8)-specific mRNA were found in the B220^-CD4⁺ cells and B220⁺CD4⁺ cells as compared with normal B220^-CD4⁺ cells, while V(β8)-specific mRNA was preferentially expressed only by B220⁺CD4^-CD8^- cells. Either B220⁺CD4⁺ cells and B220⁺CD4^-CD8^- cells failed to respond to anti-CD3 monoclonal antibody (MoAb) as assessed by proliferative responses and production of interleukin-2 (IL-2). However, appreciable levels of reactivity to anti-CD3 MoAb were detected in the B220^-CD4⁺ cells, although the responsiveness of this subset to such stimuli were reduced, compared with those of normal control. These results indicate that the B220^-CD4⁺ cells in lpr mice are phenotypically and functionally distinct from normal B220^-CD4⁺ cells.