Differential remodeling of a T-cell transcriptome following CD8- versus CD3-induced signaling

Abidi SH, Dong T, Vuong MT, Sreenu VB, Rowland-Jones SL, Evans EJ, Davis SJ. (2008), Cell Res. 18, 641-8

Abstract

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.

Key figure: Comparison of transcripts whose expression in clone 32 is affected by anti-CD8 and anti-CD3 antibody treatments

Each line in the plots represents a unique SAGE tag sequence, colored according to the fold change in its relative abundance in the antibody-treated library indicated at the top of the column compared to that in the resting clone 32-derived library. Coloring is on a log base 2 scale, as shown in the key below panel C. Bracketed regions are referred to in the text. In (A), all 2 472 tags that are significantly differentially abundant in either comparison are listed, and sorted according to the fold change in abundance in the anti-CD3 antibody-treated library compared to the resting cell-derived library. In (B), only the subset of those tags from (A) that have been assigned to a transcript encoding a protein of known function are included and they are sorted first by the functional class of this protein, then by the fold change in abundance in the library derived from anti-CD3 antibody-treated clone 32 cells versus those derived from resting clone 32 cells, as in (A). Codes used for the functional classes are as follows: SF, secreted factors; CS, cell surface molecules; S, cytoplasmic signaling molecules; T, transcriptional regulation; AP, antigen presentation; CC, cell cycle and survival; CT, cytoskeleton and vesicle transport; P, protein synthesis; and O, other function, including many metabolic enzymes and other housekeeping genes. (C and D) identify all the tags from (B) linked to secreted factors and proteins involved in transcriptional regulation, respectively. In these panels, the common abbreviation for the protein encoded by the transcript linked to the tag is given alongside. If a protein name appears twice, two SAGE tags associated with its transcript were significantly differentially expressed in one of the comparisons. The numerical values of the changes in abundance for all the SAGE tags used in this figure, together with their sequence and the description of all UniGene clusters automatically linked to them, are available in Supplementary information, Spreadsheet 1.