The appearance of T cells bearing self-reactive T cell receptor in the livers of mice injected with bacteria.
We demonstrated in the present study that with bacterial stimulation, an increased number of alpha/beta T cells proliferated in the liver of mice and that even T cells bearing self-reactive T cell receptor (TCR) (or forbidden T cell clones), as estimated by anti-V beta monoclonal antibodies in conjunction with immunofluorescence tests, appeared in the liver and, to some extent, in the periphery. The majority (greater than 80%) of forbidden clones induced had double-negative CD4-8-phenotype. In a syngeneic mixed lymphocyte reaction, these T cells appear to be self-reactive. Such forbidden clones and normal T cells in the liver showed a two-peak pattern of TCR expression, which consisted of alpha/beta TCR dull and bright positive cells, as seen in the thymus. A systematic analysis of TCR staining patterns in the various organs was then carried out. T cells from not only the thymus but also the liver had the two-peak pattern of alpha/beta TCR, whereas all of the other peripheral lymphoid organs had a single-peak pattern of TCR. However, T cells in the liver were not comprised of double-positive CD4+8+ cells, which predominantly reside in the thymus. The present results therefore suggest that T cell proliferation in the liver might reflect a major extrathymic pathway for T cell differentiation and that this hepatic pathway has the ability to produce T cells bearing self-reactive TCR under bacterial stimulation, probably due to the lack of a double-positive stage for negative selection.
Abo
T
T
Department of Microbiology, Tohoku University School of Dentistry, Sendai, Japan.
Ohteki
T
T
Seki
S
S
Koyamada
N
N
Yoshikai
Y
Y
Masuda
T
T
Rikiishi
H
H
Kumagai
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D004926:Escherichia coli / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D011425:Propionibacterium acnes / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell