title: Superantigen-induced CD4 memory T cell anergy. I. Staphylococcal enterotoxin B induces Fyn-mediated negative signaling.
abstract: Memory CD4 T cells must provide robust protection for an organism while still maintaining self-tolerance. Superantigens reveal a memory cell-specific regulatory pathway, by which signaling through the TCR can lead to clonal tolerance (anergy). Here we show that the src kinase Fyn is a critical regulator of anergy in murine memory CD4 T cells induced by the bacterial superantigen staphylococcal enterotoxin B (SEB). Exposure to SEB results in impaired TCR signaling due to failed CD3/ZAP-70 complex formation. Further, signal transduction through the TCR remains similarly blocked when anergic memory cells are subsequently exposed to agonist peptide antigen. Pharmacological inhibition or genetic elimination of Fyn kinase reverses memory cell anergy, resulting in SEB-induced cell proliferation. The mechanism underlying impaired TCR signaling and subsequent memory cell anergy must involve a Fyn signaling pathway given that the suppression of Fyn activity restores CD3/ZAP-70 complex formation and TCR proximal signaling.
authors.affiliation: The Department of Biomedical Sciences, The School of Public Health, The University at Albany, Albany, NY 12201-0509, United States.
authors.forename: Andrew R O
authors.initials: AR
authors.lastname: Watson
authors.forename: David K
authors.initials: DK
authors.lastname: Janik
authors.forename: William T
authors.initials: WT
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D018345:Mice, Knockout; D050721:Proto-Oncogene Proteins c-cbl / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013210:Staphylococcus / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004768:Enterotoxins; C491468:Fyb protein, mouse; D011948:Receptors, Antigen, T-Cell; C031818:enterotoxin B, staphylococcal; D050721:Proto-Oncogene Proteins c-cbl; C493849:Cbl protein, mouse