title: IL-4 producing CD4+ TCR alpha beta int liver lymphocytes: influence of thymus, beta 2-microglobulin and NK1.1 expression.
abstract: The present report describes developmental, phenotypic and functional features of unconventional CD4+ TCR alpha beta lymphocytes. In C57BL/6 mice, the majority of liver lymphocytes expressing intermediate intensity of TCR alpha beta (TCR alpha beta int) are CD4+ NK1.1+ and express a highly restricted TCR V beta repertoire, dominated by V beta 8 with some contribution by V beta 7 and V beta 2. Although these cells express the CD4 co-receptor, they are present in H2-1 A beta (A beta)-/- gene disruption mutants but are markedly reduced in beta 2-microglobulin (beta 2m)-/- mutant mice and hence are beta 2m dependent. Thymocytes expressing the CD4+ NK1.1+ TCR alpha beta phenotype are also beta 2m contingent, suggesting that these two T lymphocyte populations are related. The CD4+ NK1.1+ TCR alpha beta lymphocytes in liver and thymus share several markers such as LFA-1+, CD44+, CD5+, LECAM-1- and IL-2R alpha-. The CD4+ NK1.1+ TCR alpha beta int liver lymphocytes were not detected in athymic nu/nu mice. We conclude that beta 2m expression is crucial for development of the CD4+ NK1.1+ TCR alpha beta int liver lymphocytes and that thymus plays a major role. CD4+ TCR alpha beta int liver lymphocytes were also identified in NK1.1- mouse strains, there lacking the NK1.1 marker. We assume that the NK1.1 molecule is a characteristic marker of the CD4+ TCR alpha beta int liver lymphocytes in NK1.1+ mouse strains, although its expression is not obligatory for their development. The liver lymphocytes from beta 2m+/-, but not from beta 2m-/-, mice are potent IL-4 producers in response to CD3 or TCR alpha beta engagement and the IL-4 production by liver lymphocytes was markedly reduced by treatment with anti-NK1.1 mAb. We conclude that the CD4+ NK1.1+ TCR alpha beta int liver lymphocytes are capable of producing IL-4 in response to TCR stimulation.
authors.affiliation: Department of Immunology, University of Ulm, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Emoto
authors.forename: Y
authors.initials: Y
authors.lastname: Emoto
authors.forename: S H
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D000941:Antigens / Q000096:biosynthesis / Q000502:physiology*; D000950:Antigens, Ly; D000954:Antigens, Surface; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000378:metabolism*; D005260:Female; D006183:H-2 Antigens / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D055651:NK Cell Lectin-Like Receptor Subfamily B; D014176:Protein Biosynthesis; D011506:Proteins / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin; D015847:Interleukin-4