We have examined the level of surface expression and functional properties of leukocyte function associated antigen-1, very late antigen-4, and CD45 isoforms on a panel of human CD4+ T-cell clones representative of TH0, TH1, and TH2 cells. There were no qualitative differences in the expression of these antigens among the three types of CD4+ T-cell clones. However, CD45RB was the only CD45 isoform that provided a costimulatory signal in a solid-phase antibody-induced cellular proliferation assay. Additionally, the antigen-induced proliferative response of T-cell clones was inhibited by soluble anti-CD45RO and anti-CD45RB antibodies. Our results suggest that CD45 isoforms differentially provide costimulatory signals to T cells. However, the ability of each CD45 isoform to provide a costimulatory signal does not differ among the TH0, TH1, or TH2 T-cell populations.