Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion

Proceedings of the National Academy of Sciences of the United States of America

Volumn 115, Issue 10, 2018, Pages 2455-2460

  Avery, Lyndsay ^a,b   Filderman, Jessica ^b   Szymczak Workman, Andrea L ^a   Kane, Lawrence P ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

Chronic infection; Co stimulation; LCMV; mTOR; T cell exhaustion

Indexed keywords

HEPATITIS A VIRUS CELLULAR RECEPTOR 2; HAVCR2 PROTEIN, MOUSE; LYMPHOCYTE ANTIGEN RECEPTOR; MTOR PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE;

AKT/MTOR SIGNALING; ANIMAL EXPERIMENT; ANIMAL MODEL; ARENAVIRUS INFECTION; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVATION; LIMIT OF QUANTITATION; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; LYMPHOCYTIC CHORIOMENINGITIS VIRUS INFECTION; MEMORY T LYMPHOCYTE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; T CELL EXHAUSTION; T LYMPHOCYTE ACTIVATION; UPREGULATION; VIRUS STRAIN; WESTERN BLOTTING; ANIMAL; CHRONIC DISEASE; GENETICS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; LYMPHOCYTIC CHORIOMENINGITIS; METABOLISM; PHENOTYPE; SIGNAL TRANSDUCTION; T LYMPHOCYTE SUBPOPULATION;

ANIMALS; CHRONIC DISEASE; HEPATITIS A VIRUS CELLULAR RECEPTOR 2; LYMPHOCYTE ACTIVATION; LYMPHOCYTIC CHORIOMENINGITIS; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; MICE; PHENOTYPE; RECEPTORS, ANTIGEN, T-CELL; SIGNAL TRANSDUCTION; T-LYMPHOCYTE SUBSETS; TOR SERINE-THREONINE KINASES;

EID: 85042914346     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1712107115     Document Type: Article

References (38)

1. Monney L, et al. (2002) Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature 415:536–541.
2. Wherry EJ (2011) T cell exhaustion. Nat Immunol 12:492–499.
3. Pauken KE, Wherry EJ (2015) Overcoming T cell exhaustion in infection and cancer. Trends Immunol 36:265–276.
4. Zajac AJ, et al. (1998) Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med 188:2205–2213.
5. Gorman JV, Colgan JD (2014) Regulation of T cell responses by the receptor molecule Tim-3. Immunol Res 59:56–65.
6. Anderson AC, Joller N, Kuchroo VK (2016) Lag-3, Tim-3, and TIGIT: Co-inhibitory receptors with specialized functions in immune regulation. Immunity 44:989–1004.
7. Du W, et al. (2017) TIM-3 as a target for cancer immunotherapy and mechanisms of action. Int J Mol Sci 18:E645.
8. + T cell function by multiple costimulatory receptors during chronic HIV infection. J Immunol 185:3007–3018.
9. Vali B, et al. (2010) HCV-specific T cells in HCV/HIV co-infection show elevated frequencies of dual Tim-3/PD-1 expression that correlate with liver disease progression. Eur J Immunol 40:2493–2505.
10. + HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity. J Clin Invest 120:4546–4557.
11. Jin HT, et al. (2010) Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci USA 107:14733–14738.
12. + T cell dysfunction in melanoma patients. J Exp Med 207: 2175–2186.
13. Sakuishi K, et al. (2010) Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med 207:2187–2194.
14. + T cells in human tuberculosis (TB) exhibit polarized effector memory phenotypes and stronger anti-TB effector functions. PLoS Pathog 8:e1002984.
15. Gorman JV, et al. (2014) Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection. J Immunol 192:3133–3142.
16. Lee J, et al. (2011) Phosphotyrosine-dependent coupling of Tim-3 to T-cell receptor signaling pathways. Mol Cell Biol 31:3963–3974.
17. Phong BL, et al. (2015) Tim-3 enhances FceRI-proximal signaling to modulate mast cell activation. J Exp Med 212:2289–2304.
18. Anderson AC, et al. (2007) Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science 318:1141–1143.
19. Han G, Chen G, Shen B, Li Y (2013) Tim-3: An activation marker and activation limiter of innate immune cells. Front Immunol 4:449.
20. Nakae S, et al. (2007) TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells. Blood 110:2565–2568.
21. Zikherman J, Parameswaran R, Weiss A (2012) Endogenous antigen tunes the responsiveness of naive B cells but not T cells. Nature 489:160–164.
22. Sánchez-Fueyo A, et al. (2003) Tim-3 inhibits T helper type 1-mediated auto- and al-loimmune responses and promotes immunological tolerance. Nat Immunol 4:1093–1101.
23. Wherry EJ, Barber DL, Kaech SM, Blattman JN, Ahmed R (2004) Antigen-independent memory CD8 T cells do not develop during chronic viral infection. Proc Natl Acad Sci USA 101:16004–16009.
24. + T cell differentiation. Nat Rev Immunol 12:749–761.
25. Barber DL, et al. (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439:682–687.
26. Maekawa Y, et al. (2008) Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity. Nat Immunol 9:1140–1147.
27. + T cell fate by regulating the expression of transcription factors T-bet and eomesodermin. Immunity 32:67–78.
28. + T cells is hampered by persistent systemic antigen, but full functional capacity is regained in an antigen-free environment. J Immunol 172:6074–6079.
29. Zhu C, et al. (2005) The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol 6:1245–1252.
30. Ferris RL, Lu B, Kane LP (2014) Too much of a good thing? Tim-3 and TCR signaling in T cell exhaustion. J Immunol 193:1525–1530.
31. Araki K, et al. (2009) mTOR regulates memory CD8 T-cell differentiation. Nature 460: 108–112.
32. + T cells. Virology 425:122–132.
33. Jones RB, et al. (2008) Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection. J Exp Med 205: 2763–2779.
34. Hand TW, et al. (2010) Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival. Proc Natl Acad Sci USA 107:16601–16606.
35. Macintyre AN, et al. (2011) Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism. Immunity 34: 224–236.
36. Ahmed R, Salmi A, Butler LD, Chiller JM, Oldstone MB (1984) Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice: Role in suppression of cytotoxic T lymphocyte response and viral persistence. J Exp Med 160:521–540.
37. McCausland MM, Crotty S (2008) Quantitative PCR technique for detecting lymphocytic choriomeningitis virus in vivo. J Virol Methods 147:167–176.
38. + T cell differentiation: Initial antigen encounter triggers a developmental program in naïve cells. Nat Immunol 2:415–422.