Programmed cell death 1 and Helios distinguish TCR-αβ+ double-negative (CD4-CD8-) T cells that derive from self-reactive CD8 T cells.

Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1550-6606 (Electronic) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE

Publication: Bethesda, MD : American Association of Immunologists
Original Publication: Baltimore : Williams & Wilkins, c1950-

CD8-Positive T-Lymphocytes/*cytology ; CD8-Positive T-Lymphocytes/*immunology ; DNA-Binding Proteins/*metabolism ; Programmed Cell Death 1 Receptor/*metabolism ; Receptors, Antigen, T-Cell, alpha-beta/*metabolism ; T-Lymphocyte Subsets/*cytology ; T-Lymphocyte Subsets/*metabolism ; Transcription Factors/*metabolism; Animals ; Mice ; Mice, Nude ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; T-Lymphocyte Subsets/immunology

TCR-αβ(+) double-negative (DN; CD4(-)CD8(-)) T cells represent a poorly understood cellular subset suggested to contribute to the pathogenesis of the autoimmune disease systemic lupus erythematosus. DN T cells have been proposed to derive from CD8(+) cells. However, the conditions that govern the loss of CD8 expression after Ag encounter are unknown. In this study, we tracked the fate of CD8 T cells from transgenic TCR mice exposed to their cognate Ags as self or in the context of infection. We demonstrate that CD8 T cells lose CD8 expression and become DN only when cognate Ag is sensed as self. This process is restricted to tissues where the Ag is present. We also show that DN T cells derived from self-reactive CD8 cells express the inhibitory molecules PD-1 and Helios. These molecules identify a subset of DN T cells in normal mice. A similar population expands when CD8 T cells from repertoires enriched in self-reactive cells (Aire-deficient) are transferred into cognate hosts. Collectively, our data suggest that a subset of DN T cells, identified by the expression of PD-1 and Helios, represent self-reactive cells. Our results provide an explanation for the origin of DN T cells and introduce CD8 loss as a process associated with self-Ag encounter.
(Copyright © 2015 by The American Association of Immunologists, Inc.)

Nat Immunol. 2004 Jun;5(6):597-605. (PMID: 15133507)
J Immunol. 2006 Sep 1;177(5):2803-9. (PMID: 16920915)
J Immunol. 1984 Apr;132(4):1809-13. (PMID: 6142069)
Nature. 1988 Jun 23;333(6175):742-6. (PMID: 3260350)
J Immunol. 1989 Jul 1;143(1):103-12. (PMID: 2525144)
Science. 1991 Mar 8;251(4998):1225-8. (PMID: 1900951)
Cell. 1991 Apr 19;65(2):293-304. (PMID: 1849799)
Science. 1993 Jun 18;260(5115):1802-5. (PMID: 8511588)
J Immunol. 1993 Jul 15;151(2):1086-96. (PMID: 7687614)
Immunity. 1994 Aug;1(5):405-13. (PMID: 7882171)
J Immunol. 1995 May 15;154(10):4986-95. (PMID: 7537297)
Immunity. 1995 Nov;3(5):541-7. (PMID: 7584144)
J Exp Med. 1996 Sep 1;184(3):923-30. (PMID: 9064352)
J Exp Med. 1997 Jul 21;186(2):239-45. (PMID: 9221753)
J Immunol. 1998 Aug 15;161(4):1686-93. (PMID: 9712032)
Blood. 2007 May 1;109(9):4071-9. (PMID: 17197428)
J Clin Invest. 2007 May;117(5):1361-9. (PMID: 17446931)
J Immunol. 2010 Feb 15;184(4):1710-20. (PMID: 20083652)
Trends Mol Med. 2010 Feb;16(2):47-57. (PMID: 20138006)
Arthritis Rheum. 2010 Jun;62(6):1702-11. (PMID: 20178125)
J Clin Invest. 2011 Jun;121(6):2221-41. (PMID: 21537078)
Nat Immunol. 2011 Jun;12(6):492-9. (PMID: 21739672)
PLoS One. 2012;7(5):e37042. (PMID: 22590644)
Nat Med. 2012 Jul;18(7):1069-76. (PMID: 22772566)
Immunity. 2012 Dec 14;37(6):1130-44. (PMID: 23159438)
J Exp Med. 2013 Jun 3;210(6):1153-65. (PMID: 23650440)
J Exp Med. 2013 Sep 23;210(10):1911-8. (PMID: 23980099)
Cell Immunol. 2013 Jul-Aug;284(1-2):68-74. (PMID: 23933188)
J Biol Chem. 2014 Jan 24;289(4):2361-70. (PMID: 24297179)
J Immunol. 2014 May 1;192(9):4134-44. (PMID: 24683191)
J Autoimmun. 2014 Jun;51:38-43. (PMID: 24461537)
Eur J Immunol. 2014 Jul;44(7):2048-58. (PMID: 24740292)
Lupus. 2002;11(8):501-7. (PMID: 12220104)
Science. 2002 Nov 15;298(5597):1395-401. (PMID: 12376594)
Nat Genet. 2002 Dec;32(4):666-9. (PMID: 12402038)
J Virol. 2003 Apr;77(8):4911-27. (PMID: 12663797)
Am J Transplant. 2003 Nov;3(11):1355-62. (PMID: 14525595)
J Immunol. 2007 Oct 15;179(8):5064-70. (PMID: 17911591)
J Exp Med. 2007 Oct 29;204(11):2667-77. (PMID: 17954566)
PLoS One. 2008;3(1):e1512. (PMID: 18231598)
Nat Rev Immunol. 2008 Jun;8(6):467-77. (PMID: 18500231)
Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17475-80. (PMID: 18988742)
J Immunol. 2008 Dec 15;181(12):8761-6. (PMID: 19050297)
Nat Immunol. 2009 Jan;10(1):29-37. (PMID: 19043418)
Arthritis Rheum. 2009 Jan;60(1):207-18. (PMID: 19116915)
Cancer Immunol Immunother. 2009 May;58(5):709-18. (PMID: 18836718)
J Immunol. 2009 Oct 1;183(7):4675-81. (PMID: 19734235)
Nat Med. 2000 Jul;6(7):782-9. (PMID: 10888927)
J Exp Med. 2000 Oct 2;192(7):1027-34. (PMID: 11015443)
Kidney Int. 2001 Aug;60(2):664-71. (PMID: 11473649)
J Immunol. 2004 Feb 1;172(3):1602-11. (PMID: 14734741)
Am J Pathol. 1998 Nov;153(5):1541-50. (PMID: 9811346)
Science. 1999 May 14;284(5417):1187-91. (PMID: 10325233)
J Immunol. 1999 Jul 1;163(1):155-64. (PMID: 10384112)
J Exp Med. 2005 Jul 4;202(1):111-21. (PMID: 15998791)
Nature. 2006 Feb 9;439(7077):682-7. (PMID: 16382236)
Immunity. 2004 Sep;21(3):391-400. (PMID: 15357950)

R01 AI085567 United States AI NIAID NIH HHS; R21 AR063262 United States AR NIAMS NIH HHS; T32 AI007387 United States AI NIAID NIH HHS

0 (DNA-Binding Proteins)
0 (Pdcd1 protein, mouse)
0 (Programmed Cell Death 1 Receptor)
0 (Receptors, Antigen, T-Cell, alpha-beta)
0 (Transcription Factors)
0 (Zfpn1a2 protein, mouse)

Date Created: 20150401 Date Completed: 20150720 Latest Revision: 20181113

20240829

PMC4503929

10.4049/jimmunol.1402775

25825451