Class I-Restricted T Cell-Associated Molecule Is a Marker for IFN-γ-Producing iNKT Cells in Healthy Subjects and Patients with Type 1 Diabetes.
Class I-restricted T cell-associated molecule (CRTAM) is an activation marker expressed on the cell surface of activated invariant natural killer T (iNKT) cells, CD8+T cells, and a small subset of CD4+T cells. CRTAM has also been associated with a proinflammatory profile in murine CD4+T cells. However, CRTAM has not been thoroughly explored in human cells. This work focused on evaluating CRTAM expression in human iNKT lymphocytes after activation with α-galactosylceramide, its widely used specific glycolipid antigen. We also analyzed the involvement of costimulatory molecules in CRTAM expression and whether CRTAM expression is associated with a specific effector cytokine profile. We found that the signal produced by invariant T cell receptor (iTCR) engagement with α-galactosylceramide is sufficient to trigger CRTAM expression on human iNKT cells after 18 h of stimulation. Moreover, we observed a clear association between CRTAM expression and IFN-γ production in iNKT cells from healthy subjects and patients with type 1 diabetes. However, blocking the engagement of costimulatory molecules, such as CD40, CD80, and CD86, did not modify CRTAM expression. These results indicate that CRTAM may also play a role in triggering the production of IFN-γ in human iNKT cells and that CRTAM could be used as a marker to identify these inflammatory cells.
1 Department of Molecular Biomedicine, Center for Research and Advanced Studies (CINVESTAV) , Mexico City, Mexico .
Nonantzin
N
Beristain-Covarrubias
2 Laboratory of Zoonoses, Dr. Hideyo Noguchi Center for Regional Investigations, Autonomous University of Yucatan , Merida, Mexico .
Elsy B
EB
Canche-Pool
3 Department of Allergy, Dr. Fernando Quiroz Gutierrez General Hospital , ISSSTE, Mexico City, Mexico .
Carlos
C
Ramirez-Velazquez
1 Department of Molecular Biomedicine, Center for Research and Advanced Studies (CINVESTAV) , Mexico City, Mexico .
Juan Carlos
JC
Barragan-Galvez
4 Research Unit on Clinical Epidemiology (UMAE), Specialty Hospital, National Medical Center , IMSS, Mexico City, Mexico .
Rita A
RA
Gomez-Diaz
1 Department of Molecular Biomedicine, Center for Research and Advanced Studies (CINVESTAV) , Mexico City, Mexico .
Vianney
V
Ortiz-Navarrete
D015415:Biomarkers; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis*; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D015415:Biomarkers; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007136:Immunoglobulins; D018836:Inflammation Mediators; C408522:class-I restricted T cell-associated molecule; D007371:Interferon-gamma
CRTAM; IFN-γ; Necl-2; iNKT cells; type 1 diabetes