The regulation of CD4 T cell numbers during an immune response should take account of the amount of antigen (Ag), the initial frequency of Ag-specific T cells, the mix of naive versus experienced cells, and (ideally) the diversity of the repertoire. Here we describe a novel mechanism of T cell regulation that potentially deals with all of these parameters. We found that CD4 T cells establish a negative feedback loop by capturing their cognate MHC/peptide complexes from Ag-presenting cells and presenting them to Ag-experienced CD4 T cells, thereby inhibiting their recruitment into the response while allowing recruitment of naive T cells. The inhibition is Ag specific, begins at day 2 (long before Ag disappearance), and cannot be overcome by providing new Ag-loaded dendritic cells. In this way CD4 T cell proliferation is regulated in a functional relationship to the amount of Ag, while allowing naive T cells to generate repertoire variety.
ASJC Scopus subject areas
- Cell Biology
Helft, J., Jacquet, A., Joncker, N. T., Grandjean, I., Dorothée, G., Kissenpfennig, A., Malissen, B., Matzinger, P., & Lantz, O. (2008). Antigen-specific T-T interactions regulate CD4 T-cell expansion. Blood, 112(4), 1249-1258. https://doi.org/10.1182/blood-2007-09-114389