Altered function in CD8+ T cells following paramyxovirus infection of the respiratory tract.
For many respiratory pathogens, CD8+ T cells have been shown to play a critical role in clearance. However, there are still many unanswered questions with regard to the factors that promote the most efficacious immune response and the potential for immunoregulation of effector cells at the local site of infection. We have used infection of the respiratory tract with the model paramyxovirus simian virus 5 (SV5) to study CD8+ T-cell responses in the lung. For the present study, we report that over time a population of nonresponsive, virus-specific CD8+ T cells emerged in the lung, culminating in a lack of function in approximately 85% of cells specific for the immunodominant epitope from the viral matrix (M) protein by day 40 postinfection. Concurrent with the induction of nonresponsiveness, virus-specific cells that retained function at later times postinfection exhibited an increased requirement for CD8 engagement. This change was coupled with a nearly complete loss of functional phosphoprotein-specific cells, a response previously shown to be almost exclusively CD8 independent. These studies add to the growing evidence for immune dysregulation following viral infection of the respiratory tract.
Gray
Peter M
PM
Department of Microbiology & Immunology, Room 5108, Gray Building, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Arimilli
Subhashini
S
Palmer
Ellen M
EM
Parks
Griffith D
GD
Alexander-Miller
Martha A
MA
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D045402:Parainfluenza Virus 5 / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D019351:Rubulavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D014763:Viral Matrix Proteins / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D000956:Antigens, Viral; D000939:Epitopes; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D007371:Interferon-gamma
J Immunol. 1999 Nov 15;163(10):5535-43
10553081
J Exp Med. 1998 May 18;187(10):1647-57
9584143
J Exp Med. 1998 Dec 21;188(12):2205-13
9858507
J Exp Med. 1999 Jan 18;189(2):423-34
9892624
J Virol. 2000 Jul;74(13):5769-75
10846055
Cell Immunol. 2000 May 25;202(1):13-22
10873302
Eur J Immunol. 2001 Feb;31(2):412-20
11180105
J Immunol. 2001 Feb 1;166(3):1813-22
11160228
J Exp Med. 2001 Mar 5;193(5):F19-22
11238597
J Immunol. 2001 Apr 1;166(7):4604-11
11254718
Swiss Med Wkly. 2001 Apr 7;131(13-14):171-9
11345807
Nat Immunol. 2001 Aug;2(8):711-7
11477407
Eur J Immunol. 2001 Sep;31(9):2574-82
11536155
J Immunol. 2001 Sep 15;167(6):3293-9
11544317
J Virol. 2001 Nov;75(21):10065-72
11581375
Nat Immunol. 2001 Nov;2(11):1067-76
11668342
Nat Med. 2002 Jan;8(1):54-60
11786907
Pediatr Res. 2002 Sep;52(3):363-7
12193668
J Immunol. 2003 Jan 1;170(1):174-81
12496398
J Biol Chem. 2003 Jan 31;278(5):3257-64
12215456
J Immunol. 2003 Sep 1;171(5):2538-47
12928404
J Immunol Methods. 2003 Oct 1;281(1-2):65-78
14580882
Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14859-64
15465914
J Immunol. 1985 Aug;135(2):892-9
2409156
J Exp Med. 1989 Aug 1;170(2):499-509
2526847
J Virol. 1990 Apr;64(4):1683-9
2319650
J Immunol. 1990 May 15;144(10):3980-6
1692070
J Virol. 1990 Nov;64(11):5403-11
1976819
J Exp Med. 1991 Apr 1;173(4):849-58
1901079
Cell Immunol. 2000 Apr 10;201(1):58-62
10805974
Immunology. 1992 May;76(1):60-4
1628902
J Immunol. 1992 Aug 1;149(3):972-80
1634779
J Immunol. 1992 Aug 15;149(4):1319-25
1354233
J Virol. 1993 Feb;67(2):1044-9
8419638
Eur J Immunol. 1993 Aug;23(8):1956-62
8344359
Int Immunol. 1993 Oct;5(10):1219-28
8268129
Eur J Immunol. 1994 Nov;24(11):2691-8
7525300
J Virol. 1995 Feb;69(2):1261-4
7815502
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4102-7
8633023
J Exp Med. 1996 Sep 1;184(3):863-71
9064346
Clin Exp Immunol. 1997 Dec;110(3):447-53
9409650
Eur J Immunol. 2000 Mar;30(3):840-7
10741400