A unique unresponsive CD4+ T cell phenotype post TCR antagonism.
The functional outcomes of the T cell's interaction with the peptide:MHC complex can be dramatically altered by the introduction of a single amino acid substitution. Previous studies have described the varied effects of these altered peptide ligands (APL) on T cell responses. These outcomes of T cell interaction with an APL include the induction of clonal unresponsiveness (anergy) and inhibition of T cell responses (antagonism). The phenotype of peptide-induced anergy, i.e. low proliferation and low IL-2 production, has been extensively described, and a number of groups have demonstrated antagonism. However, the response of T cells to an agonist ligand after encountering an antagonistic stimulus has not been previously characterized. Here, we show that T cells post-antagonism fail to proliferate but produce large quantities of IL-2 upon stimulation with their wild type ligand. This unique phenotype is not due to differences in IL-2 receptor expression or rates of apoptosis, and cannot be overcome by the addition of recombinant IL-2. The response of CD4 T cells to agonist stimulation after encountering an antagonist is a novel phenotype, and is distinct from previously described forms of anergy.
Edwards
Lindsay J
LJ
Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322, USA.
Evavold
Brian D
BD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000494:pharmacology; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology
D007376:Interleukin-2; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2