Continuous in vivo activation and transient hyporesponsiveness to TcR/CD3 triggering of human gut lamina propria lymphocytes

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Abstract
Three‐color immunofluorescence and flow cytometric analysis showed that the vast majority of normal human T‐lamina propria lymphocytes (LPL) expressed high levels of the early activation antigen CD69, together with CD45R0, irrespective of their CD4, CD8 or γ/δ‐TcR phenotype, indicating that they are continuously stimulated in vivo. Importantly, measurement of cytoplasmic [Ca2+]i showed that T‐LPL had significantly higher basal [Ca2+]i levels, compared to autologous peripheral blood lymphocytes (PBL). Both cytoplasmic [Ca2+]i elevation and inositol (1, 4, 5) trisphosphate generation following CD3 cross‐linking by monoclonal antibodies in vitro were essentially abolished in T‐LPL, as compared to autologous T‐PBL. Moreover, freshly isolated LPL could be induced to proliferate by CD2‐ or CD28‐mediated signals, but not by CD3‐mediated signals. Surprisingly however, impairment in TcR/CD3‐mediated early signaling and proliferation in T‐LPL could be completely reversed by 24 h incubation of the cells at 37 °C in culture medium, a condition which allowed basal intracellular [Ca2+]i to return to levels comparable to peripheral T cells.Our data suggest that selective hyporesponsiveness to TcR/CD3‐mediated signaling may represent a transient event during continuous in vivo activation of mucosal lymphocytes.

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