Loss of SDF-1 receptor expression during positive selection in the thymus.
SDF-1 is a member of the CXC chemokines. In contrast to other chemokines that are induced by inflammation, SDF-1 is constitutively produced by stromal cells. In order to investigate the physiological roles of SDF-1, we constructed a fusion protein, SDF-1-Cgamma1, composed from murine SDF-1alpha and the constant region of human IgG. SDF-1-Cgamma1 stained EL-4 T lymphoma cells and the staining was blocked by rhSDF-1beta. The expression levels of SDF-1R altered along with the T cell maturation. Most c-kit+ hematopoietic precursors in fetal liver in gestational day (GD) 14.5 embryo were SDF-1R-, while c-kit+ double-negative (DN) thymocytes in the embryo were positive for SDF-1R. The receptor expression increased along with T cell maturation up to double-positive (DP) cell stage. Interestingly, SDF-1R expression was down-modulated after positive selection; CD69+CD3hi DP and CD3hi single-positive thymocytes were SDF-1R-/lo. Northern blot analysis demonstrated that SDF-1 and CXCR4 mRNAs were abundantly expressed in the thymuses of embryo and adult mice. These results demonstrate that SDF-1R expression is involved in T cell development in the thymus, particularly in positive selection.
Suzuki
G
G
Division of Radiation Health, National Institute of Radiological Sciences, Chiba, Japan.
Nakata
Y
Y
Dan
Y
Y
Uzawa
A
A
Nakagawa
K
K
Saito
T
T
Mita
K
K
Shirasawa
T
T
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001665:Binding Sites; D001667:Binding, Competitive; D015152:Blotting, Northern; D001853:Bone Marrow / Q000196:embryology / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007142:Immunoglobulin gamma-Chains / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000196:embryology / Q000276:immunology; D008223:Lymphoma; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D007142:Immunoglobulin gamma-Chains; D019718:Receptors, CXCR4; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D019009:Proto-Oncogene Proteins c-kit