Selective antigen presenting activity of cortical thymic epithelial cells against CD4+ T cells associated with both lack of costimulatory molecules and inefficient presentation of MHC-peptide ligands.
Selective activation among several effector functions of a T cell clone, DB14, specific for pigeon cytochrome c 43-58 (p43-58) and restricted to I-Ab/d was induced by antigen (Ag) presentation with nonprofessional Ag-presenting cells (APC), cortical thymic epithelial cells (c-TEC) (B7-1- CD40-), whereas full activation of the DB14 was induced with another nonprofessional APC, I-Ab L cell (B7-1+ CD40+). In the present study, to elucidate the mechanism underlying the selective activation of DB14 cells by c-TEC, we established c-TEC transfected with human CD40 alone (huCD40-c-TEC) or both human CD40 and murine B7-1 (huCD40/mB7-1-c-TEC), and compared the APC functions with those of the original c-TEC and I-Ab L cell. IFN-gamma production but not the proliferative response of DB14 was elevated by Ag presentation with huCD40-c-TEC as compared with unmanipulated c-TEC. On the other hand, upon stimulation with Ag plus huCD40/mB7-1-c-TEC both a significant proliferative response and IFN-gamma production were induced in DB14. However, the level of these responses did not reach that induced in the presence of I-Ab L cell. A similar pattern of APC functions was demonstrated with the other B7-independent T cell clone, PAB3, or T cell hybridomas (DBhy22 and BD7-5) which are basically independent of costimulation for the activation. The present finding along with our previous report that several structural differences of I-Ab molecules are present between c-TEC and I-Ab L cell suggests that the distinct APC activity of c-TEC is attributable not only to a lack of B7-1 and CD40 but also to inefficient presentation of MHC-peptide complex on the c-TEC.
Kaneda
R
R
Section of Pathology, Hokkaido University, Sapporo, Japan.
Iwabuchi
K
K
Kasai
M
M
Murakami
M
M
Uede
T
T
Onoé
K
K
D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004847:Epithelial Cells / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D007739:L Cells; D008213:Lymphocyte Activation; D051379:Mice; D011994:Recombinant Proteins / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology; D014162:Transfection
D018122:B7-1 Antigen; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D007519:Isoantigens; D011994:Recombinant Proteins; D007371:Interferon-gamma