Thymic epithelial cells responsible for impaired generation of NK-T thymocytes in Alymphoplasia mutant mice.
We have previously shown that the generation of an NK1.1+TCRalphabeta+ (NK-T) cell population is severely impaired in an alymphoplasia mutant (aly/aly) mouse strain and the defect resides in the thymic environment. In the present study, to elucidate the thymic stromal component(s) that affects the development of NK-T cells, radiation bone marrow chimeras were established with the aly/aly mouse as a donor and either the beta2 microglobulin knockout (beta2m-/-) or the CD1d1-/- mouse that also lacks the NK-T cell population as a recipient. A normal population of NK-T cells with a typical NK-T phenotype and functions was detected in both the thymus and the spleen of these chimeras. These findings indicated that a radiation-resistant CD1(-) component of the thymus supported generation of functional NK-T cells from aly/aly precursors. Furthermore, transfer of an intact medullary thymic epithelial cell line into aly/aly thymus significantly induced the generation of NK-T cells in the thymus. These findings suggest that CD1 molecules of bone marrow-derived cells and the medullary epithelial cells acted in concert in the generation of the NK-T cell population and that a function(s) of the medullary thymic epithelial cells other than direct presentation of CD1 molecules to the NK-T precursors is indispensable for the development of NK-T cells.
Konishi
J
J
Division of Immunobiology, Hokkaido University, Kita-15, Nishi-7, Kita-Ku, Sapporo 060-0815, Japan.
Iwabuchi
K
K
Iwabuchi
C
C
Ato
M
M
Nagata
J I
JI
Onoé
K
K
Nakagawa
K I
KI
Kasai
M
M
Ogasawara
K
K
Kawakami
K
K
Onoé
K
K
D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics; D055610:Antigens, CD1d; D001854:Bone Marrow Cells / Q000502:physiology; D002460:Cell Line / Q000637:transplantation; D017637:Clonal Deletion; D004847:Epithelial Cells / Q000473:pathology / Q000637:transplantation; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D011828:Radiation Chimera; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000473:pathology; D017154:Stromal Cells / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology* / Q000637:transplantation; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D018949:Antigens, CD1; D055610:Antigens, CD1d; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin; D015847:Interleukin-4