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Mice lacking protein tyrosine kinase fyn develop a T helper-type 1 response and resistLeishmania major infection

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Environmental Health and Preventive Medicine Aims and scope

Abstract

Fyn is a Src family protein tyrosine kinase associated with TCR/CD3 complex. Fyn appears to play a role in the activation of T cells based on its enzymatic activation and tyrosine phosphorylation following the ligation of TCR/CD3, and it also plays a critical role in the calcium flux and interleukin-2 (IL-2) production. The protective response against murineLeishmania major infection is associated with the T helper-type 1 (Th1) responses and the ability to modulate Th1 cytokines such as IL-2 and interferon-γ, respectively. The role of Fyn tyrosine kinasein vivo was directly examined by the response to infection withL. major in C57BL/6fyn-deficient mice. Despite the absence of Fyn, the mice remained resistant to this infection with only mild lesion development, and, they demonstrated Th1 responses as assessed by the delayed-type hyper-sensitivity response and cytokine milieu. The findings in thefyn-deficient mice failed to support a relationship between the anticipated functions of Fynin vitro and the immune response toL. major infectionin vivo. As a result, in leishmanial disease, Fyn probably plays a minor role in the protective immune response and is, therefore, not a key factor in such a response.

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References

  1. Reiner SL, Locksley RM. The regulation of immunity toLeishmania major. Annu. Rev. Immunol. 1995; 13: 151–177.

    Article  PubMed  CAS  Google Scholar 

  2. Güler ML, Jacobson NG, Gubler U, Murphy KM. T cell genetic background determines maintenance of IL-12 signaling: Effects on BALB/c and B10.D2 T helper cell type 1 phenotype development. J. Immunol. 1997; 159: 1767–1774.

    PubMed  Google Scholar 

  3. Scharton-Kersten T, Afonso LCC, Wysocka M, Trinchieri G, Scott P. IL-12 is required for natural killer cell activation and subsequent T helper 1 cell development in experimental leishmaniasis. J. Immunol. 1995; 154: 5320–5330.

    PubMed  CAS  Google Scholar 

  4. Kropf P, Etges R, Schopf L, Chung C, Sypek J, Müller I. Characterization of T cell-mediated responses in nonhealing and healingLeishmania major infections in the absence of endogenous IL-4. J. Immunol. 1997; 159: 3434–3443.

    PubMed  CAS  Google Scholar 

  5. Launois P, Swihart KG, Milon G, Louis JA. Early production of IL-4 in susceptible mice infected withLeishmania major rapidly induces IL-12 unresponsiveness. J. Immunol. 1997; 158: 3317–3324.

    PubMed  CAS  Google Scholar 

  6. Raab M, Kang H, da Silva A, Zhu X, Rudd CE. FYN-T-FYB-SLP-76 interactions define a T-cell receptor zeta/CD3-mediated tyrosine phosphorylation pathway that up-regulates interleukin 2 transcription in T-cells. J. Biol. Chem. 1999; 274: 21170–21179.

    Article  PubMed  CAS  Google Scholar 

  7. Tsygankov AY, Spana C, Rowley RB, Penhallow RC, Burkhardt AL, Bolen JB. Activation-dependent tyrosine phosphorylation of fyn-associated proteins in T lumphocytes. J. Biol. Chem. 1994; 269: 7792–7800.

    PubMed  CAS  Google Scholar 

  8. Utting O, Teh SJ, Teh HS. T cells expressing receptors of different affinity for antigen ligands reveal a unique role for p59fyn in T cell development and optimal stimulation of T cells by antigen. J. Immunol. 1998; 160:5410–5419.

    PubMed  CAS  Google Scholar 

  9. Qian D, Lev S, van Oers NS, Dikie I, Schlessinger J, Weiss A. Tyrosine phosphorylation of Pyc2 is selectively regulated by Fyn during TCR signaling. J. Exp. Med. 1997; 185: 1253–1259.

    Article  PubMed  CAS  Google Scholar 

  10. Stein PL, Lee H-M, Rich S, Soriano P. pp59fyn mutant mice display diffential signaling in thymocytes and peripheral T cells. Cell 1992; 70: 741–750.

    Article  PubMed  CAS  Google Scholar 

  11. Appleby MW, Gross JA, Cooke MP, Levin SD, Qian X, Perlmutter RM. Defective T cell receptor signaling in mice lacking the thymic isoform of p59fyn. Cell 1992; 70: 751–763.

    Article  PubMed  CAS  Google Scholar 

  12. Fusaki N, Semba K, Katagiri T, Suzuki G, Matsuda S, Yamamoto T. Characterization of p59fyn-mediated signal transduction on T cell activation. Int. Immunol. 1994; 6: 1245–1255.

    Article  PubMed  CAS  Google Scholar 

  13. Tamura T, Nakano H, Nagase H, Morokata T, Igarashi O, Oshimi Y, Miyazaki S, Nariuchi H. Early activation signal transduction pathways of Th1 and Th2 cell clones stimulated with anti-CD3. Roles of protein tyrosine kinases in the signal for IL-2 and IL-4 production. J. Immunol. 1995; 155: 4692–4701.

    PubMed  CAS  Google Scholar 

  14. Lee SK, Shaw A, Maher SE, Bothwell AL. p59fyn tyrosine kinase regulates p56lck tyrosine kinase activity and early TCR-mediated signaling. Int. Immunol. 1994; 6: 1621–1627.

    Article  PubMed  CAS  Google Scholar 

  15. Criado G, Feito MJ, Rojo JM. CD4-dependent and-independent association of protein tyrosine kinases to the T cell receptor/CD3 complex of CD4+ mouse T lymphocytes. Eur. J. Immunol. 1996; 26: 1228–1234.

    Article  PubMed  CAS  Google Scholar 

  16. Fusaki N, Matsuda S, Nishizumi H, Umemori H, Yamamoto T. Physical and functional interractions of protein tyrosine kinases, p59fyn and ZAP-70, in T cell signaling. J. Immunol. 1996; 156: 1369–1377.

    PubMed  CAS  Google Scholar 

  17. Groves T, Smiley P, Cooke MP, Forbush K, Perlmutter RM, Guidos CJ. Fyn can partially substitute for Lck in T lymphcyte development. Immunity 1996; 5: 417–428.

    Article  PubMed  CAS  Google Scholar 

  18. Wong J, Straus D, Chan AC. Genetic evidence of a role for lck in T-cell receptor function independent or downstream of ZAP-70/Syk protein tyrosine kinases. Mol. Cell Biol. 1998; 18: 2855–2866.

    PubMed  CAS  Google Scholar 

  19. Denny MF, Patai B, Straus DB. Differential T-cell antigen receptor signaling mediated by the Src family kinases lck and fyn. Mol. Cell Biol. 2000; 20: 1426–1435.

    Article  PubMed  CAS  Google Scholar 

  20. Sharton TM, Scott P. Natural killer cells are a source of interferon γ that drives differentiation of CD4; T cell subsets and induces early resistance toLeishmania major in mice. J. Exp. Med. 1993; 178: 567–577.

    Article  Google Scholar 

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Correspondence to Kazuo Yamakami.

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Yamakami, K., Akao, S., Wakabayashi, K. et al. Mice lacking protein tyrosine kinase fyn develop a T helper-type 1 response and resistLeishmania major infection. Environ Health Prev Med 6, 132–135 (2001). https://doi.org/10.1007/BF02897960

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  • DOI: https://doi.org/10.1007/BF02897960

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