Induction of T-cell hyporesponsiveness by intrahepatic modulation of donor antigen-presenting cells.
In this study, we examined the ability of varying populations of donor cells from B6 mice to induce hyporesponsiveness in T lymphocytes from C3H mice in vitro and in vivo. Small, resting B lymphocytes were inefficient stimulators of T-lymphocyte proliferation compared to splenic mononuclear cells (SMNC) and lipopolysaccharide (LPS)-induced B-cell blasts in vitro (P < 0.05). Pretreatment of SMNC with anti-B7-1 or anti-intracellular adhesion molecule-1 (ICAM-1) monoclonal antibodies (mAb) similarly resulted in inefficient stimulation of T-cell proliferation in vitro (P < 0.05). However, in vivo, only intrahepatic, but not intravenous, injection of donor cells into C3H mice resulted in decreased T-lymphocyte proliferation in response to restimulation by alloantigen. This effect was most pronounced following intrahepatic injection of resting B lymphocytes or SMNC pretreated with anti-ICAM-1 mAb compared to uninjected or intravenously injected mice (P < 0.05). The hyporesponsiveness was associated with an increased production of interleukin-4 (IL-4) by the responder T lymphocytes and correlated with enhanced skin allograft survival. These data demonstrate that intrahepatic injection of donor-derived cells induces T-lymphocyte hyporesponsiveness. The mechanism appears to be modulated by an ICAM-1-mediated signal resulting in expansion of an IL-4-producing T-lymphocyte population.
Chung
S W
SW
Department of Surgery, Toronto Hospital, University of Toronto, Canada.
Gorczynski
R M
RM
Dziadkowiec
I
I
Levy
G A
GA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D005260:Female; D006085:Graft Survival / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D007519:Isoantigens / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008099:Liver / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
D018122:B7-1 Antigen; D007519:Isoantigens; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4