title: T cells stimulated with an analog peptide of type II collagen require the Fc receptor γ-chain to secrete interleukin-4 and suppress autoimmune arthritis in mice.
abstract: OBJECTIVE
  To explore the characteristics of the T cell population that responds to an analog peptide (A9) of type II collagen and regulates autoimmunity, using the collagen-induced arthritis (CIA) model.
  
  
  METHODS
  Analog peptide A9 is a 26-amino acid peptide analogous to the sequence of a segment of type II collagen (CII245-270) but with substitutions at amino acid positions 260 (alanine for isoleucine), 261 (hydroxyproline for alanine), and 263 (asparagine for phenylalanine). We previously showed that A9 profoundly suppressed CIA and immune responses to type II collagen. In order to determine the mechanism of suppression, we used transgenic mice whose T cells express a type II collagen-specific receptor (T cell receptor) and performed passive cell transfer experiments.
  
  
  RESULTS
  The results demonstrated that suppression of CIA by A9 is dependent on T cells. Using multiparameter flow cytometry, we determined that the cells responsible for suppression were CD4+ and expressed high levels of Fcε receptor Iγ chain (FcRγ). To establish the significance of this finding, we obtained mice genetically deficient in FcRγ in order to perform passive transfer experiments. The resulting FcRγ-/- CD4+ T cells, when primed by culture with A9, could not transfer the suppression of arthritis or secrete cytokines in response to A9.
  
  
  CONCLUSIONS
  Taken together, the results of this study suggest that the suppression of arthritis and the Th2 cytokine profile elicited by A9 is dependent on the presence of FcRγ in T cells. These findings are novel and may have therapeutic potential for patients with autoimmune arthritis.
authors: University of Tennessee, Memphis, TN 38163, USA. lmyers@uthsc.edu
authors: Linda K
authors: LK
authors: Myers
authors: David L
authors: DL
authors: Cullins
authors: David D
authors: DD
authors: Brand
authors: Sandra
authors: S
authors: Kleinau
authors: John M
authors: JM
authors: Stuart
authors: Andrew H
authors: AH
authors: Kang
references: J Mol Med (Berl). 2001 Oct;79(10):552-65
references: 11692152
references: Nat Med. 2000 Oct;6(10):1167-75
references: 11017150
references: J Immunol. 1993 May 15;150(10):4652-8
references: 8482852
references: Clin Immunol. 2009 Oct;133(1):145-53
references: 19596610
references: Clin Immunol. 2002 Feb;102(2):185-91
references: 11846461
references: Crit Rev Immunol. 2007;27(4):345-56
references: 18197813
references: Curr Pharm Des. 2003;9(23):1861-70
references: 12871190
references: Curr Protoc Immunol. 2010 Apr;Chapter 15:Unit 15.5.1-25
references: 20376842
references: J Exp Med. 2004 Jan 5;199(1):25-34
references: 14699080
references: J Immunol. 2007 Jul 1;179(1):409-20
references: 17579062
references: Nat Med. 2000 Oct;6(10):1176-82
references: 11017151
references: Annu Rev Immunol. 2010;28:445-89
references: 20192806
references: Nat Immunol. 2010 Mar;11(3):197-206
references: 20139988
references: J Exp Med. 2000 May 1;191(9):1611-6
references: 10790435
references: J Immunol. 2008 Dec 1;181(11):8145-52
references: 19018007
references: J Immunol. 2002 Jan 1;168(1):490-8
references: 11751997
references: Arthritis Res Ther. 2005;7(3):93
references: 15899057
references: Arthritis Rheum. 2009 Nov;60(11):3207-16
references: 19877047
references: Clin Immunol. 2002 Aug;104(2):105-14
references: 12165271
references: Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4228-33
references: 15024101
references: Arthritis Res. 1999;1(1):81-91
references: 11056663
references: J Immunol. 1998 Oct 1;161(7):3589-95
references: 9759881
references: J Immunol. 2001 Mar 1;166(5):3499-505
references: 11207309
references: Clin Vaccine Immunol. 2010 Apr;17(4):618-25
references: 20107011
references: Eur J Immunol. 2003 Aug;33(8):2269-77
references: 12884302
references: J Immunol. 2001 Oct 1;167(7):3545-9
references: 11564763
references: J Immunol. 2004 Jun 15;172(12):7821-31
references: 15187166
references: J Immunol. 2006 Aug 15;177(4):2250-7
references: 16887985
references: Annu Rev Immunol. 2006;24:209-26
references: 16551248
references: J Immunol. 1972 Mar;108(3):586-90
references: 4401006
references: Life Sci. 1997;61(19):1861-78
references: 9364191
references: J Immunol. 2003 Oct 1;171(7):3325-31
references: 14500623
references: Immunology. 2008 Jan;123(1):40-4
references: 18154618