Host T-cell primary allosensitization to MHC class-I- and class-II-expressing human cardiac myocytes requires the presence of a second signal.
Normal FHCMs, or transformed cell lines derived from FHCMs, such as W1, even after induction of MHC antigens by pretreatment with IFN-gamma, failed to induce proliferation of allogeneic human PBMCs in vitro. To test the hypothesis that antigen-specific T-cell activation and proliferation require not only the binding of the TCR with its ligand, the MHC molecule, but also a second signal that involves the interaction of T-cell surface molecules with their natural ligands on the stimulating cells, a mAb against CD28 was used. Cocultures of allogeneic PBMCs with IFN-gamma-pretreated irradiated FHCMs or the W1 cell line in microtiter plates containing immobilized anti-CD28 mAb induced marked stimulator cells MHC class-II-specific proliferative responses. The W1 cell line and FHCMs failed to express detectable levels of the BB1/B7 molecule (the natural ligand for CD28) as determined by flow microfluorometry or mRNA levels coding for BB1/B7 as determined by RT-PCR. These data suggest that one of the probably reasons for the failure of MHC-expressing cardiac myocytes to induce allogeneic activation is the absence of costimulatory signals.
Ansari
A A
AA
Winship Cancer Center, Atlanta, GA 30322.
Wang
Y C
YC
Kanter
K
K
Villinger
F
F
Mayne
A
A
Sell
K W
KW
Herskowitz
A
A
D001483:Base Sequence; D018106:CD28 Antigens / Q000276:immunology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D005333:Fetus; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007519:Isoantigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018106:CD28 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens