Human CD45RA+ and CD45R0+ T cells exhibit similar CD3/T cell receptor-mediated transmembrane signaling capacities but differ in response to co-stimulatory 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.
Schwinzer
R
R
Klinik für Abdominal- and Transplantationschirurgie, Medizinische Hochschule, Hannover, FRG.
Siefken
R
R
Franklin
R A
RA
Saloga
J
J
Wonigeit
K
K
Gelfand
E W
EW
D000938:Antigen-Presenting Cells / Q000502:physiology; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D017493:Leukocyte Common Antigens / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism
D007376:Interleukin-2; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D014443:Tyrosine; D011493:Protein Kinase C; D017493:Leukocyte Common Antigens