Expression of the CD7 ligand K-12 in human thymic epithelial cells: regulation by IFN-gamma.
CD7 is an immunoglobulin superfamily molecule expressed on T, NK, and pre-B lymphocytes. Previous studies have demonstrated a role for CD7 in T- and NK-cell activation and cytokine production. Recently, an epithelial cell secreted protein, K12, was identified as a CD7 ligand. Although CD7 is expressed intrathymically, it is not known if K12 is produced in human thymus. To determine roles that K12 might play in the human thymus, we analyzed expression of K12 in human thymocytes, thymic epithelial cells (TE), and thymic fibroblasts. We found that recombinant human K12 bound strongly to soluble hCD7, with a Keq of 37.6x10(-9) M, and this interaction was inhibited by a novel antihuman K12 monoclonal antibody (K12-A1). K12 mRNA was detected by RT-PCR and northern analysis in human TE and thymic fibroblasts, but not in human thymocytes. Expression of K12 in TE cells was upregulated by IFN-gamma. Taken together, these data demonstrated that K12 is produced by human TE cells and thymic fibroblasts, and is regulated in thymus by IFN-gamma. These data suggest a role for thymic microenvironment-produced K12 in regulation of thymocyte signaling and cytokine release, particularly in the setting of thymus pathology where IFN-gamma is upregulated such as myasthenia gravis.
Lam
Gordon K
GK
Department of Medicine, Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Liao
Hua-Xin
HX
Xue
Yan
Y
Alam
S Munir
SM
Scearce
Richard M
RM
Kaufman
Russel E
RE
Sempowski
Gregory D
GD
Haynes
Barton F
BF
D000911:Antibodies, Monoclonal / Q000302:isolation & purification; D019011:Antigens, CD7 / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D019011:Antigens, CD7; D008565:Membrane Proteins; D011994:Recombinant Proteins; C111200:SECTM1 protein, human; D007371:Interferon-gamma
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