IL-10 Directly Suppresses CD4 but Not CD8 T Cell Effector and Memory Responses Following Acute Viral Infection

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Feb 6

PMID 20133700

Citations 85

Authors

David G Brooks

Kevin B Walsh

Heidi Elsaesser

Michael B A Oldstone

Affiliations

Soon will be listed here.

Abstract

Mounting effective T cell responses is critical for eliciting long-lasting immunity following viral infection and vaccination. A multitude of inhibitory and stimulatory factors are induced following infection, and it is the compilation of these signals that quantitatively and qualitatively program the ensuing effector and memory T cell response. In response to lymphocytic choriomeningitis virus (LCMV) infection, the immunosuppressive cytokine IL-10 is rapidly up-regulated; however, how IL-10 is regulating what is often considered an "optimal" immune response is unclear. We demonstrate that IL-10 directly inhibits effector and memory CD4 T cell responses following an acutely resolved viral infection. Blockade of IL-10 enhanced the magnitude and the functional capacity of effector CD4 T cells that translated into increased and more effective memory responses. On the other hand, lack of IL-10 signaling did not impact memory CD8 T cell development. We propose that blockade of IL-10 may be an effective adjuvant to specifically enhance CD4 T cell immunity and protection following vaccination.

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References

Barber D, Wherry E, Masopust D, Zhu B, Allison J, Sharpe A . Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2005; 439(7077):682-7. DOI: 10.1038/nature04444. View

Blackburn S, Shin H, Nicholas Haining W, Zou T, Workman C, Polley A . Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol. 2008; 10(1):29-37. PMC: 2605166. DOI: 10.1038/ni.1679. View

Folgori A, Spada E, Pezzanera M, Ruggeri L, Mele A, Garbuglia A . Early impairment of hepatitis C virus specific T cell proliferation during acute infection leads to failure of viral clearance. Gut. 2006; 55(7):1012-9. PMC: 1856340. DOI: 10.1136/gut.2005.080077. View

Kaech S, Hemby S, Kersh E, Ahmed R . Molecular and functional profiling of memory CD8 T cell differentiation. Cell. 2003; 111(6):837-51. DOI: 10.1016/s0092-8674(02)01139-x. View

Yi J, Du M, Zajac A . A vital role for interleukin-21 in the control of a chronic viral infection. Science. 2009; 324(5934):1572-6. PMC: 2736049. DOI: 10.1126/science.1175194. View

Mege J, Meghari S, Honstettre A, Capo C, Raoult D . The two faces of interleukin 10 in human infectious diseases. Lancet Infect Dis. 2006; 6(9):557-69. DOI: 10.1016/S1473-3099(06)70577-1. View

Steinbrink K, Wolfl M, Jonuleit H, Knop J, Enk A . Induction of tolerance by IL-10-treated dendritic cells. J Immunol. 1997; 159(10):4772-80. View

Oxenius A, Bachmann M, Zinkernagel R, Hengartner H . Virus-specific MHC-class II-restricted TCR-transgenic mice: effects on humoral and cellular immune responses after viral infection. Eur J Immunol. 1998; 28(1):390-400. DOI: 10.1002/(SICI)1521-4141(199801)28:01<390::AID-IMMU390>3.0.CO;2-O. View

Rigopoulou E, Abbott W, Haigh P, Naoumov N . Blocking of interleukin-10 receptor--a novel approach to stimulate T-helper cell type 1 responses to hepatitis C virus. Clin Immunol. 2005; 117(1):57-64. DOI: 10.1016/j.clim.2005.06.003. View

10.

Rosenberg E, Billingsley J, Caliendo A, Boswell S, Sax P, Kalams S . Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science. 1997; 278(5342):1447-50. DOI: 10.1126/science.278.5342.1447. View

11.

Thimme R, Oldach D, Chang K, Steiger C, Ray S, Chisari F . Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med. 2001; 194(10):1395-406. PMC: 2193681. DOI: 10.1084/jem.194.10.1395. View

12.

Marzo A, Klonowski K, Le Bon A, Borrow P, Tough D, Lefrancois L . Initial T cell frequency dictates memory CD8+ T cell lineage commitment. Nat Immunol. 2005; 6(8):793-9. PMC: 2849311. DOI: 10.1038/ni1227. View

13.

Brooks D, Teyton L, Oldstone M, McGavern D . Intrinsic functional dysregulation of CD4 T cells occurs rapidly following persistent viral infection. J Virol. 2005; 79(16):10514-27. PMC: 1182641. DOI: 10.1128/JVI.79.16.10514-10527.2005. View

14.

Borrow P, Evans C, Oldstone M . Virus-induced immunosuppression: immune system-mediated destruction of virus-infected dendritic cells results in generalized immune suppression. J Virol. 1995; 69(2):1059-70. PMC: 188677. DOI: 10.1128/JVI.69.2.1059-1070.1995. View

15.

Cacciarelli T, Martinez O, Gish R, VILLANUEVA J, Krams S . Immunoregulatory cytokines in chronic hepatitis C virus infection: pre- and posttreatment with interferon alfa. Hepatology. 1996; 24(1):6-9. DOI: 10.1002/hep.510240102. View

16.

Groux H, Bigler M, De Vries J, Roncarolo M . Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells. J Exp Med. 1996; 184(1):19-29. PMC: 2192687. DOI: 10.1084/jem.184.1.19. View

17.

Matloubian M, Concepcion R, Ahmed R . CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection. J Virol. 1994; 68(12):8056-63. PMC: 237269. DOI: 10.1128/JVI.68.12.8056-8063.1994. View

18.

Ejrnaes M, Filippi C, Martinic M, Ling E, Togher L, Crotty S . Resolution of a chronic viral infection after interleukin-10 receptor blockade. J Exp Med. 2006; 203(11):2461-72. PMC: 2118120. DOI: 10.1084/jem.20061462. View

19.

Day C, Seth N, Lucas M, Appel H, Gauthier L, Lauer G . Ex vivo analysis of human memory CD4 T cells specific for hepatitis C virus using MHC class II tetramers. J Clin Invest. 2003; 112(6):831-42. PMC: 193667. DOI: 10.1172/JCI18509. View

20.

Surh C, Sprent J . Homeostasis of naive and memory T cells. Immunity. 2008; 29(6):848-62. DOI: 10.1016/j.immuni.2008.11.002. View