Development of CD4-CD8- alpha beta TCR+NK1.1+ T lymphocytes: thymic selection by self antigen.
Development of CD4-CD8- double negative (DN) alpha beta TCR+ cells were examined by cell transfer experiments using an Ly-5 congenic mouse system. Purified DN alpha beta TCR+ thymocytes injected intrathymically emigrated from the thymus to the spleen. The same cells did not return to the thymus when injected i.v. Similarly, peripheral DN alpha beta TCR+ cells from spleen and liver did not go to the thymus when injected i.v. but migrated to the spleen. These results indicate that DN alpha beta TCR+ thymocytes develop within the thymus and emigrate to peripheral organs. It is thus likely that peripheral DN alpha beta TCR+ cells are at least partly of thymic origin. DN alpha beta TCR+ thymocytes are unique in that they express a natural killer cell marker, NK1.1, which is not found on conventional T cells. We further examined the thymic selection of DN alpha beta TCR+NK1.1+ thymocytes by using an anti-HY TCR-transgenic (tg)/Rag-2(-/-) mouse system with H-2 backgrounds that were negative, positive, or nonselecting for conventional T cells. The number of DNtg TCR alpha beta+NK1.1+ cells was m prominent in male H-2b animals in which conventional T cells are deleted by HY/H-2Db recognition. Fewer DNtg TCR alpha beta+NK1.1+ cells were found in H-2b females (positive selecting background), and almost no DNtg TCR alpha beta+NK1.1+ cells were detected in H-2d animals (nonselecting background). Unlike conventional T cells, DNtg TCR alpha beta+NK1.1+ cells from anti-HY/Rag-2(-/-) H-2b mice express Fc(epsilon)RI(gamma) and CD3zeta as DN alpha beta TCR+NK1.1+ cells from normal C57BL/6 mice. Our results indicate that DNtg TCR alpha beta+NK1.1+ cells are positively selected by self Ag/MHC and emigrate to the peripheral organs.
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
R J
RJ
Schulz
A
A
Parkes
E
E
Mizoguchi
A K
AK
Bhan
S
S
Koyasu
D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000941:Antigens / Q000032:analysis* / Q000276:immunology; D000950:Antigens, Ly; D000954:Antigens, Surface; D001324:Autoantigens / Q000276:immunology / Q000494:pharmacology*; D001483:Base Sequence / Q000235:genetics; D015704:CD4 Antigens / Q000032:analysis* / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D005260:Female; D006651:Histocytochemistry; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000032:analysis* / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000276:immunology; D017455:Receptors, IgE / Q000096:biosynthesis; D012641:Selection, Genetic; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D001324:Autoantigens; D015704:CD4 Antigens; D016827:CD8 Antigens; 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; D017455:Receptors, IgE