Afferent and efferent pathways in T cell responses to MHC class I+, II-hepatocytes.
We have previously reported that purified hepatocytes stimulate significant in vitro allospecific cytotoxicity when cocultured with naive responder splenocytes in the mixed lymphocyte hepatocyte culture (MLHC). In this report we examined the expression of MHC antigens on the surface of hepatocytes, the phenotypic lymphocyte subset(s) that respond(s) to allogeneic hepatocytes, and the phenotype of allospecific cytolytic effectors generated in MLHC. Hepatocytes expressed MHC class I but not MHC class II antigens by immunofluorescent microscopy and fluorescence activated cell sorting. The lack of MHC class II on the surface of hepatocytes was also indirectly supported by the inability of hepatocytes to stimulate proliferation of a class II-directed allospecific helper T cell clone. The generation of allospecific cytotoxicity in MLHC required the participation of L3T4+, Ly2- T cells and L3T4-, Ly2+ T cells in the naive responder splenocyte population since depletion of these subsets with mAb and complement abrogated the development of allo-CTLs. Furthermore, adherent accessory cells in the naive responder splenocyte population appeared to play a role in the generation of allospecific cytotoxicity in MLHC since depletion of this population by plastic adherence and passage through a Sephadex G10 column resulted in significantly reduced allospecific cytotoxicity. Depletion of day 5 allosensitized cells of Ly2+ but not L3T4+ T cells by mAb and complement eliminated allospecific cytotoxicity--indicating that cytolytic effectors generated in MLHC appear to be L3T4-, Ly2+ T cells.
Bumgardner
G L
GL
Department of Surgery, University of Minnesota, Minneapolis 55455.
Chen
S
S
Hoffman
R
R
Cahill
D C
DC
So
S K
SK
Platt
J
J
Bach
F H
FH
Ascher
N L
NL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006183:H-2 Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D014176:Protein Biosynthesis; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II