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Expression and Function of TLR2 on CD4 Versus CD8 T Cells

  • Lee, Sun-Mi (Departments of Microbiology and Immunology, College of Medicine, Inje University) ;
  • Joo, Young-Don (Departments of Hemato/Oncology, College of Medicine, Inje University) ;
  • Seo, Su-Kil (Departments of Microbiology and Immunology, College of Medicine, Inje University)
  • Received : 2009.07.24
  • Accepted : 2009.08.18
  • Published : 2009.08.31

Abstract

Background: Toll-like receptors (TLRs) play a fundamental role in innate immunity through their capacity to recognize pathogen-associated molecular patterns. Also, TLRs that are expressed in T cells are reported to function as co-stimulatory receptors. However, the functional capacity of TLRs on CD4 T and CD8 T cells has not been directly compared. Here we compared CD4 and CD8 T cell responses to TLR2 ligand plus TCR-mediated stimulation. Methods: TLR2 expression was analyzed on T cell subsets under naive and alloantigen-primed conditions. We analyzed the effects of TLR2 co-stimulation on proliferation and survival of T cell subsets in vitro when stimulated with soluble anti-CD3 in the presence or absence of synthetic ligand $Pam_3CSK_4$. Results: TLR2 expression on CD8 T cells was induced following activation; this expression was much higher than on CD4 T cells. Thus, the molecule was constitutively expressed on Listeriaspecific memory CD8 T cells. Based on these expression levels, proliferation and survival were markedly elevated in CD8 T cells in response to the TLR2 co-stimulation by $Pam_3CSK_4$ compared with those in CD4 T cells. Conclusion: Our data show that TLR2 co-stimulation is more responsible for proliferation and survival of CD8 T cells than for that of CD4 T cells.

Keywords

References

  1. Takeda K, Kaisho T, Akira S: Toll-like receptors. Annu Rev Immunol 21;335-376, 2003 https://doi.org/10.1146/annurev.immunol.21.120601.141126
  2. Medzhitov R: Toll-like receptors and innate immunity. Nat Rev Immunol 1;135-145, 2001 https://doi.org/10.1038/35100529
  3. Komai-Koma M, Jones L, Ogg GS, Xu D, Liew FY: TLR2 is expressed on activated T cells as a costimulatory receptor. Proc Natl Acad Sci USA 101;3029-3034, 2004 https://doi.org/10.1073/pnas.0400171101
  4. Gelman AE, Zhang J, Choi Y, Turka LA: Toll-like receptor ligands directly promote activated CD4+ T cell survival. J Immunol 172;6065-6073, 2004 https://doi.org/10.4049/jimmunol.172.10.6065
  5. Gelman AE, LaRosa DF, Zhang J, Walsh PT, Choi Y, Sunyer JO, Turka LA: The adaptor molecule MyD88 activates PI-3 kinase signaling in CD4+ T cells and enables CpG oligodeoxynucleotide-mediated costimulation. Immunity 25;783-793, 2006 https://doi.org/10.1016/j.immuni.2006.08.023
  6. Imanishi T, Hara H, Suzuki S, Suzuki N, Akira S, Saito T: Cutting edge: TLR2 directly triggers Th1 effector functions. J Immunol 178;6715-6719, 2007 https://doi.org/10.4049/jimmunol.178.11.6715
  7. Cottalorda A, Verschelde C, Mar\varsigmaais A, Tomkowiak M, Musette P, Uematsu S, Akira S, Marvel J, Bonnefoy-Berard N: TLR2 engagement on CD8 T cells lowers the threshold for optimal antigen-induced T cell activation 36;1684-1693,2006 https://doi.org/10.1002/eji.200636181
  8. Quigley M, Martinez J, Huang X, Yang Y: A critical role for direct TLR2-MyD88 signaling in CD8 T-cell clonal expansion and memory formation following vaccinia viral infection. Blood 113;2256-2264, 2009 https://doi.org/10.1182/blood-2008-03-148809
  9. Rahman AH, Cui W, Larosa DF, Taylor DK, Zhang J, Goldstein DR, Wherry EJ, Kaech SM, Turka LA: MyD88 plays a critical T cell-intrinsic role in supporting CD8 T cell expansion during acute lymphocytic choriomeningitis virus infection. J Immunol 181;3804-3810, 2008 https://doi.org/10.4049/jimmunol.181.6.3804
  10. Asprodites N, Zheng L, Geng D, Velasco-Gonzalez C, Sanchez-Perez L, Davila E: Engagement of Toll-like receptor-2 on cytotoxic T-lymphocytes occurs in vivo and augments antitumor activity. FASEB J 22;3628-3637, 2008 https://doi.org/10.1096/fj.08-108274
  11. Shuford WW, Klussman K, Tritchler DD, Loo DT, Chalupny J, Siadak AW, Brown TJ, Emswiler J, Raecho H, Larsen CP, Pearson TC, Ledbetter JA, Aruffo A, Mittler RS: 4-1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J Exp Med 186;47-55, 1997 https://doi.org/10.1084/jem.186.1.47
  12. Marsland BJ, Kopf M: Toll-like receptors: paving the path to T cell-driven autoimmunity? Curr Opin Immunol 19;611-614, 2007 https://doi.org/10.1016/j.coi.2007.07.022
  13. Wong P, Pamer EG: CD8 T cell responses to infectious pathogens. Annu Rev Immunol 21;29-70, 2003 https://doi.org/10.1146/annurev.immunol.21.120601.141114
  14. Dougan M, Dranoff G: Immune therapy for cancer. Annu Rev Immunol 27;83-117, 2009 https://doi.org/10.1146/annurev.immunol.021908.132544
  15. Wong P, Lara-Tejero M, Ploss A, Leiner I, Pamer EG: Rapid development of T cell memory. J Immunol 172;7239-7245, 2004 https://doi.org/10.4049/jimmunol.172.12.7239
  16. Steinman RM, Hawiger D, Nussenzweig MC: Tolerogenic dendritic cells. Annu Rev Immunol 21;685-711, 2003 https://doi.org/10.1146/annurev.immunol.21.120601.141040
  17. Kerfoot SM, Long EM, Hickey MJ, Andonegui G, Lapointe BM, Zanardo RC, Bonder C, James WG, Robbins SM, Kubes P: TLR4 contributes to disease-inducing mechanisms resulting in central nervous system autoimmune disease. J Immunol 173;7070-7077, 2004 https://doi.org/10.4049/jimmunol.173.11.7070
  18. Lee EK, Kang SM, Paik DJ, Kim JM, Youn J: Essential roles of toll-like receptor 4 signaling in arthritis induced by type II collagen antibody and LPS. Int Immunol 17;325-333, 2005 https://doi.org/10.1093/intimm/dxh212
  19. Meng G, Rutz M, Schiemann M, Metzger J, Grabiec A, Schwandner R, Luppa PB, Ebel F, Busch DH, Bauer S, Wagner H, Kirschning CJ: Antagonistic antibody prevents toll-like receptor 2-driven lethal shock-like syndromes. J Clin Invest 113:1473-1481, 2004 https://doi.org/10.1172/JCI20762

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