What Scales the T Cell Response?

Abstract

T cells are known to scale their clonal expansion and effector cytokine response according to the dose and strength of antigenic signal so as to balance their role of affecting protection with the intertwined and immunologically driven tissue damage. How T cells achieve this is now beginning to be understood. We underscore temporal integration of digital T cell receptor (TCR) signaling as the basis for achieving scaled response by means of accumulating crucial mediators over time. We also discuss the role of temporally integrated crosstalk between TCR and IL2 signaling in mediating a scaled, coherent, collective response by T cells. Finally, we highlight numerous known and putative regulatory interactions in the transcriptional program that are expected to quantitatively scale the T cell response, and also offer new mechanisms to hitherto unexplained observations.

Human CD8+T cells exhibit a shared antigen threshold for different effector responses

“…1B). A digital switch has been reported in the TCR signalling pathway (10,11) and a large number of T cell responses, including cytokine production, have been shown to be digital (31,38,39). Therefore, the observation that the induction of different cytokines have a comparable antigen threshold implies that they have comparable TCR signalling thresholds, and it is likely that they share a common rate-limiting switch.…”

Lymphocytic division clocked up by Myc

“…In particular, it currently remains unclear how to bridge the large time separation between signal transduction and subsequent cell divisions. [6][7][8][9] Naive lymphocyte Taking the broader view, this study by Heinzel et al illustrates the strength of quantitative analysis in immunology. The Hodgkin group originally defined DD as a new immunological parameter, 3 of critical relevance for T-cell expansion.…”

“…Heinzel et al 's study challenges the community to decipher how Myc levels are fine‐tuned so that input signals robustly determine lymphocytic division destiny. In particular, it currently remains unclear how to bridge the large time separation between signal transduction and subsequent cell divisions 6 , 7 , 8 , 9 …”

Vaccination with a codon-optimized A27L-containing plasmid decreases virus replication and dissemination after vaccinia virus challenge

“…This suggests that Imiquimod did not enhance the induction of immune responses in these set of experiments. We speculate that the intense immune response produced after vaccination with the optimized plasmid, at some point triggers a regulatory effect when combined with the adjuvant as a result of excessive epitope levels (45–48). We interpret this effect to induce either a higher rate of signal decay or to establish a top ceiling in the increase of the signals obtained from the adjuvanted group compared to non-adjuvanted mice.…”