HUMAN CD45RA+ AND CD45R0+ T-CELLS EXHIBIT SIMILAR CD3/T CELL RECEPTOR-MEDIATED TRANSMEMBRANE SIGNALING CAPACITIES BUT DIFFER IN RESPONSE TO COSTIMULATORY SIGNALS

CD45RA(+) cells have been described to be less responsive to CD3/T cell receptor (TcR)-mediated activation than CD45R0(+) T cells. To analyze the underlying mechanism of the differential responses we compared CD3/TcR-triggered tyrosine phosphorylation in the two subsets and studied the role of co-stimulatory signals provided either by accessory cells or pharmacologic activation of protein kinase C by phorbol ester. Stimulation of purified CD45RA(+) and CD45R0(+) T cells with CD3/TcR antibodies induced similar patterns and intensities of tyrosine phosphorylation in the two subsets, but no proliferation. If accessory cells were used as the source of co-stimulatory signals, strong expression of the 55-kDa chain of the interleukin-2. (IL-2) receptor (CD25), significant IL-2 production and vigorous proliferation were observed in CD45R0(+) cells, whereas CD45RA(+) cells responded weakly. However, when CD3/TcR-mediated triggering was combined with activation of protein kinase C by phorbol ester, CD45RA(+) cells responded strongly. These data indicate that the transmembrane signaling capacity of the T cell receptor expressed by CD45RA(+) and CD45R0(+) cells is similar and, therefore, is presumably not responsible for the differential reactivities of the two subsets. It is more likely that co-stimulatory signals determine whether CD3/TcR-initiated activation results in strong or weak responses.