Selection of phenotypically distinct NK1.1+ T cells upon antigen expression in the thymus or in the liver.
Unlike the main TCR alphabeta T cell lineage in which deletion occurs at the CD4+ CD8+ double-positive (DP) stage upon TCR engagement by antigen in the thymus, some T cells appear to require such engagement for their selection, either in the thymus or extrathymically. We used a transgenic TCR (tgTCR) model which, as we previously showed, led to selection upon expression of the corresponding antigen H-2Kb (Kb) in the thymus, of tgTCR/CD3(lo) CD4- CD8- double-negative (DN) thymocytes that expressed the NK1.1 marker (NK T cells) (Curnow, S. J., et al., Immunity 1995. 3: 427). We now report that antigen expression on medullary epithelial cells of the thymus failed to select the NK T cells, whereas its expression on thymocytes did, although tgTCR DP thymocyte development was affected under both conditions. Antigen expression on hepatocytes (Alb-Kb mice) did not perturb tgTCR DP thymocyte development. No enrichment in tgTCR NK T cells was detected in the periphery, except for the liver of the Alb-Kb/tgTCR mice. When reconstitution of thymectomized and irradiated H-2k hosts expressing or not Kb was performed with bone marrow from tgTCR H-2k mice, an enrichment in tgTCR+ NK T cells was found in the liver, but not in the spleen, of the hosts which expressed Kb, either selectively on hepatocytes or ubiquitously. Surprisingly, the majority of the hepatic tgTCR+ NK T cells also expressed the CD8 alpha/beta heterodimer. These results indicate that thymus-independent NK T cells with unique phenotypic characteristics can be selected upon antigen encounter in the liver.
Legendre
V
V
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Parc Scientifique de Luminy, Marseille, France.
Boyer
C
C
Guerder
S
S
Arnold
B
B
Hämmerling
G
G
Schmitt-Verhulst
A M
AM
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D000950:Antigens, Ly; D000954:Antigens, Surface; D001853:Bone Marrow / Q000276:immunology; D016827:CD8 Antigens / Q000378:metabolism; D006183:H-2 Antigens / Q000235:genetics / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D037181:Lectins, C-Type; D008099:Liver / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D055651:NK Cell Lectin-Like Receptor Subfamily B; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D016827:CD8 Antigens; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D018960:Hyaluronan Receptors; 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; D015375:Receptors, Interleukin-2