Antigen-specific T-T interactions regulate CD4 T-cell expansion.
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 major histocompatibility class (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.
Laboratoire d'Immunologie Clinique, Inserm U653, Institut Curie, Paris.
Julie
J
Helft
Alexandra
A
Jacquet
Nathalie T
NT
Joncker
Isabelle
I
Grandjean
Guillaume
G
Dorothée
Adrien
A
Kissenpfennig
Bernard
B
Malissen
Polly
P
Matzinger
Olivier
O
Lantz
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D025461:Feedback, Physiological / Q000276:immunology*; D005260:Female; D006649:Histocompatibility Antigens; D007111:Immunity, Cellular; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets
D006649:Histocompatibility Antigens