Only dull CD3+ thymocytes bind to thymic epithelial cells. The binding is elicited by both CD2/LFA-3 and LFA-1/ICAM-1 interactions.
In view of the necessity for thymocytes to interact with thymic epithelial cells to differentiate into mature T cells, this study analyzed the binding between human thymocytes, cultured thymic epithelial cells (CTEC) and the required adhesion molecules. Immediately after separation, thymic epithelial cells (TEC) readily expressed ICAM-1, which is one of the ligands of LFA-1 cell adhesion molecules. However, the ICAM-1 expression was gradually lost upon culture of TEC. IFN-gamma re-induced ICAM-1 on the CTEC, and the ability of CTEC to bind to thymocytes was also increased by IFN-gamma treatment. The increase in binding seemed to be caused by the LFA-1/ICAM-1 interaction, since it was inhibited by anti-ICAM-1 monoclonal antibody (mAb) and anti-LFA-1 mAb. This suggests that the LFA-1/ICAM-1 interaction is also involved in vivo with the binding of thymocytes to TEC, which have been shown to express ICAM-1. To better understand the nature of the cells involved in binding, thymocytes were sorted into CD3-, CD3dull+, and CD3bright+ subsets (which are supposed to represent the immature, intermediate and mature stages of differentiation, respectively), and were examined for their binding to IFN-gamma-treated CTEC. The result showed that only the CD3dull+ subset bound to CTEC. CD3-, CD3bright+ cells and peripheral blood T lymphocytes did not bind, but they were induced to bind by neuramidase treatment All these bindings were inhibited by anti-LFA-1 mAb and anti-CD2 mAb. These findings indicate that CD3dull+ cells can bind to TEC via CD2/LFA-3 and LFA-1/ICAM-1 interactions. Other cells seemed not to bind to TEC because of sialylation.
Nonoyama
S
S
Department of Immunology, National Children's Medical Research Center, Tokyo, Japan.
Nakayama
M
M
Shiohara
T
T
Yata
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism* / Q000502:physiology*; D000954:Antigens, Surface / Q000378:metabolism*; D018801:CD2 Antigens; D017252:CD3 Complex; D018968:CD58 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004847:Epithelial Cells; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011971:Receptors, Immunologic / Q000378:metabolism*; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018801:CD2 Antigens; D017252:CD3 Complex; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D016028:Receptors, Leukocyte-Adhesion