Human CD45RA+ and CD45R0+ T cells exhibit similar CD3/T cell receptor‐mediated transmembrane signaling capacities but differ in response to co‐stimulatory signals

Abstract

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.