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

CD45RA(+) cells have been described to be less responsive to CD3/T cel l receptor (TcR)-mediated activation than CD45R0(+) T cells. To analyz e the underlying mechanism of the differential responses we compared C D3/TcR-triggered tyrosine phosphorylation in the two subsets and studi ed the role of co-stimulatory signals provided either by accessory cel ls or pharmacologic activation of protein kinase C by phorbol ester. S timulation of purified CD45RA(+) and CD45R0(+) T cells with CD3/TcR an tibodies induced similar patterns and intensities of tyrosine phosphor ylation in the two subsets, but no proliferation. If accessory cells w ere used as the source of co-stimulatory signals, strong expression of the 55-kDa chain of the interleukin-2. (IL-2) receptor (CD25), signif icant IL-2 production and vigorous proliferation were observed in CD45 R0(+) cells, whereas CD45RA(+) cells responded weakly. However, when C D3/TcR-mediated triggering was combined with activation of protein kin ase C by phorbol ester, CD45RA(+) cells responded strongly. These data indicate that the transmembrane signaling capacity of the T cell rece ptor expressed by CD45RA(+) and CD45R0(+) cells is similar and, theref ore, is presumably not responsible for the differential reactivities o f the two subsets. It is more likely that co-stimulatory signals deter mine whether CD3/TcR-initiated activation results in strong or weak re sponses.