Continuous in vivo activation and transient hyporesponsiveness to TcR/CD3 triggering of human gut lamina propria lymphocytes.
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 gamma/delta-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 degrees 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.
De Maria
R
R
Department of Experimental Medicine, University of Rome La Sapienza, Italy.
Fais
S
S
Silvestri
M
M
Frati
L
L
Pallone
F
F
Santoni
A
A
Testi
R
R
D002118:Calcium / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*
D017260:Receptor-CD3 Complex, Antigen, T-Cell; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium