V beta repertoire of murine hepatic T cells. Implication for selection of double negative alpha beta + T cells.
To further define the origin, selection, and diversity of hepatic T cells, we have determined V beta gene expression profiles in double negative (DN, CD4-8-) and single positive (SP, CD4+8- or CD8+4-) alpha beta + liver T cells of DBA/2 mice. These I-E+ mice express mouse mammary tumor (Mtv) provirus-encoded endogenous superantigens of the Mlsa,c type, and thus display deletions/depletions of several V beta-bearing SP cells. Total liver alpha beta + T cells of these mice exhibited an overall V beta expression profile similar to splenic T cells, with the notable exception of high V beta 7 and V beta 8.1 expression. As previously reported, DN alpha beta + T cells were enriched highly in the liver. This subset exhibited a V beta expression profile similar to thymic DN alpha beta + cells with deletions/depletions in several V beta s, but high V beta 7 expression in both populations. Surprisingly, hepatic CD4+ cells also displayed high V beta 7 expression compared with splenic T cells, suggesting that hepatic DN alpha beta + and CD4+ T cells are selected via a common pathway. The V beta 7-expressing DN alpha beta + and CD4+ liver T cell populations were polyclonal, as evidenced by cloning and sequencing. High V beta 7 expression in these cells was undiminished with age. On the basis of V beta repertoire and surface phenotype, DN alpha beta + and/or certain CD4+ T cells seem to constitute a distinct population primarily found in the liver, thymus, and bone marrow. These cells may originate from SP T cells that have down-regulated their accessory molecules under certain activation conditions and, because of the accompanying expression of particular adhesion molecules, they accumulate in tissues such as the liver and thymus.
Scripps Research Institute, Department of Immunology, La Jolla, California 92037.
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Seki
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Kono
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Balderas
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Theofilopoulos
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis*; D005260:Female; D015870:Gene Expression; D008099:Liver / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta