Down-regulation of protein kinase C activation in human lamina propria T lymphocytes: influence of intestinal mucosa on T cell reactivity.
Human lamina propria T lymphocytes (LPL-T) were shown to have lower proliferative responses to CD3 triggering than autologous peripheral blood T lymphocytes (PBL-T), yet preserved their responsiveness to CD2 stimulation. In order to elucidate the basis of these differences, freshly recovered human LPL-T and autologous PBL-T were stimulated with CD2 monoclonal antibodies anti-T11(2/3) plus sheep red blood cells and phorbol 12,13-dibutyrate (PBu2) plus ionomycin, respectively. LPL-T showed invariably lower responses to PBu2 plus ionomycin than PBL-T. In contrast, LPL-T still preserved proliferation to CD2 activation even when their responses to PBu2 plus ionomycin were decreased almost to background levels. Preincubation of PBL-T with intestinal mucosa supernatant led to a similar reactivity as observed in fresh LPL-T. Moreover, the protein kinase C (PKC) inhibitor sphinganine was able to inhibit DNA synthesis to stimulation with PBu2 plus ionomycin but not to CD2 triggering. This study suggests that CD2-induced proliferation is not dependent on PKC activation and that down-regulation of PKC activation may be one of the mechanisms for inhibition of the CD3-Ti-dependent activation pathway in LPL-T by intestinal mucosa-derived influences in vivo.
Department of Applied Immunology, University of Heidelberg, FRG.
L
L
Qiao
G
G
Schürmann
M
M
Betzler
S C
SC
Meuer
D000941:Antigens / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D018801:CD2 Antigens; D017252:CD3 Complex; D002118:Calcium / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000276:immunology*; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*
D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; D011493:Protein Kinase C; D002118:Calcium