Restoration of NK T cell development in fyn-mutant mice by a TCR reveals a requirement for Fyn during early NK T cell ontogeny.
NK T cells are a unique lymphocyte population that have developmental requirements distinct from conventional T cells. Mice lacking the tyrosine kinase Fyn have 5- to 10-fold fewer mature NK T cells. This study shows that Fyn-deficient mice have decreased numbers of NK1.1(-) NK T cell progenitors as well. 5-Bromo-2'-deoxyuridine-labeling studies indicate that the NK T cells remaining in fyn(-/-) mice exhibit a similar turnover rate as wild-type cells. The fyn(-/-) NK T cells respond to alpha-galactosylceramide, a ligand recognized by NK T cells, and produce cytokines, but have depressed proliferative capacity. Transgenic expression of the NK T cell-specific TCR alpha-chain Valpha14Jalpha18 leads to a complete restoration of NK T cell numbers in fyn(-/-) mice. Together, these results suggest that Fyn may have a role before alpha-chain rearrangement rather than for positive selection or the peripheral upkeep of cell number. NK T cells can activate other lymphoid lineages via cytokine secretion. These secondary responses are impaired in Fyn-deficient mice, but occur normally in fyn mutants expressing the Valpha14Jalpha18 transgene. Because this transgene restores NK T cell numbers, the lack of secondary lymphocyte activation in the fyn-mutant mice is due to the decreased numbers of NK T cells present in the mutant, rather than an intrinsic defect in the ability of the other fyn(-/-) lymphoid populations to respond.
Gadue
Paul
P
Graduate Group in Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yin
Liqun
L
Jain
Sumesh
S
Stein
Paul L
PL
D000818:Animals; D000941:Antigens / Q000378:metabolism; D000950:Antigens, Ly; D000954:Antigens, Surface; D016175:B-Lymphocyte Subsets / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002518:Ceramides / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D019673:Genes, T-Cell Receptor alpha; D007694:Killer Cells, Natural / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000172:deficiency / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
C116527:AGL 563; D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D002518:Ceramides; D016207:Cytokines; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D011518:Proto-Oncogene Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011505:Protein-Tyrosine Kinases; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn