Differential remodeling of a T-cell transcriptome following CD8- versus CD3-induced signaling.
CD8 engagement with class I major histocompatibility antigens greatly enhances T-cell activation, but it is not clear how this is achieved. We address the question of whether or not the antibody-mediated ligation of CD8 alone induces transcriptional remodeling in a T-cell clone, using serial analysis of gene expression. Even though it fails to induce overt phenotypic changes, we find that CD8 ligation profoundly alters transcription in the T-cell clone, at a scale comparable to that induced by antibody-mediated ligation of CD3. The character of the resulting changes is distinct, however, with the net effect of CD8 ligation being substantially inhibitory. We speculate that ligating CD8 induces weak, T-cell receptor (TCR)-mediated inhibitory signals reminiscent of the effects of TCR antagonists. Our results imply that CD8 ligation alone is incapable of activating the T-cell clone because it fails to fully induce NFAT-dependent transcription.
Abidi
S Hussain I
SH
Nuffield Department of Clinical Medicine and MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
Dong
Tao
T
Vuong
Mai T
MT
Sreenu
Vattipally B
VB
Rowland-Jones
Sarah L
SL
Evans
Edward J
EJ
Davis
Simon J
SJ
D000906:Antibodies / Q000494:pharmacology; D017252:CD3 Complex / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D002999:Clone Cells; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D015723:Gene Library; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D000906:Antibodies; D017252:CD3 Complex; D016827:CD8 Antigens; D012333:RNA, Messenger