Differential susceptibility of naive versus cloned CD4+T cells to antigen-specific and MHC-restricted anergy induction

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Journal Title:
ACTA PHYSIOLOGICA SINICA
Issue:
Volume 55, Issue 06, 2003
DOI:
Key Word:
anergy;ECDI;HNT-TCR transgenic mice;CD4 + T cell clone;proliferative response

Abstract: T cell anergy has been successfully induced under different conditions in cloned CD4 + T cells, but induction of T cell anergy in vivo has been difficult and controversial. Due to the low frequency of naturally occurring T cell population with specificity to a defined antigen, it is very difficult to study anergy of naive T cells without prior in vivo priming which complicates the interpretation of experimental data. To solve this problem, we adopted the HNT-TCR transgenic mice which have homogenous antigen specific CD4 + T cell population. In this study, we generated an influenza virus hemagglutinin (HA) peptide-specific CD4 + T cell clone from the HNT-TCR transgenic mice and induced anergy using APCs which were treated with the crosslinker, ECDI ( 1-ethyl-3-3 (3-dimethylaminopropyl) carbodiimide). The proliferative response of the cloned or freshly purified naive CD4 + transgenic T cells after treatment with ECDI-treated APCs and the HA peptide antigen was monitored as the index of anergy induction. The results showed that anergy was successfully induced in the cloned HNT-TCR transgenic CD4 + T cells. It was determined that the induced anergy was antigen- and MHC-specific. By contrast, anergy was not observed in freshly purified naive CD4 + transgenic T cells under the same conditions. The results suggest that naive CD4 + T cells may have different anergy inducing requirements, or that cloned CD4 + T cells may have certain priming or in vitro cloning artifact which makes them more susceptible to anergy induction. We propose that induction of T cell anergy may depend on the T cell growth, activation and differentiation state or cloning conditions. The results from the present study may have important implications for the study of the mechanism(s) underlying T cell anergy induction in vivo and for applications of immune tolerance based therapy.

  • [1]Lechler R, Chai J, Marelli-Berg F, Lombardi G. The induction of T-cell anergy to peripheral tolerance. Immunology 2001; 103:262 - 269.
  • [2]Schwartz RH. Models of T cell anergy: Is there a common molecular mechanism. J Exp Med 1996; 184:1 - 8.
  • [3]Jenkins MK, Schwartz R. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med 1987;165:302 - 319.
  • [4]Jenkins MK, Pardoll DM, Mizuguchi J, Quill H,Schawrtz R. T-cell unresponsiveness in vivo and in vitro:fine specificity of induction of the unresponsive state. Immunol Rev 1987 ;95:113 - 135.
  • [5]Sloan-Lancaster J, Evavoid BD, Allen PM. Induction of T-cell anergy by altered T-cell-receptor ligand on alive antigen-presenting cells. Nature 1993 ;363:156 - 159 .
  • [6]Sloan-Lancaster J, Allen PM. Altered peptide ligand-induced partial T cell activation: molecular mechanisms and role in T cell biology. Annu Rev Immunol 1996;14:1 - 27.
  • [7]Liblau RS, Pearson CI, Shokat K, Tisch R, Yang XD,McDevitt H. High-dose soluble antigen: peripheral T-cell proliferation or apoptosis. Immunol Rev 1994;142:193 - 208.
  • [8]Liblau RS, Tisch R, Shokat K, Yang XD, Dumont N,Goodnow CC, McDevitt H. Intravenous injection of soluble antigen induces thymic and peripheral T-cell apoptosis. PNAS 1996 ;93:3031 - 3036.
  • [9]Lanoue A, Bona C, Boechmer H, Sarukhan A. Conditions that induce tolerance in mature CD4 + T cells. J Exp Med 1997;185(3) :405 -414.
  • [10]Gerhard W, Haberman AM, Scherle PA, Taylor AH,Palladino G, Caton AJ. Identification of eight determinants in the hemagglutinin molecule of influenza virus A/PR/8/34 (H1N1) which are recognized by Class Ⅱ-restricted T cells from BALB/c mice. J Virol 1991 ;65:364- 372.
  • [11]Scott B, Liblau R, Degerman S, Marconi AL, Caton AJ,McDevitt HO, Lo D. A role for non-MHC genetic polymorphism in susceptibility to spontaneous antoimmunity.Immunity 1994; 1:72 - 83.
  • [12]Sytwu HK, Liblau R, McDevitt H. The role of Fas/APO-1 (CD95) and TNF in antigen-induced program cell death in T cell receptor transgenic mice. Immunity 1996 ;5:17 - 30.
  • [13]Coligan JE, Kruisbeek AM, Margulies AH, Shevach EM, Strober W. Current protocols in immunology.1992;3(13) :1 -5.
  • [14]Vandenbark AA, Barnes D, Finn T, Bourdette DN,Whitham R, Robey I, Kaleeba J, Bebo Jr BF, Miller SD, Offner H, Chou YK. Differential susceptibility of human Thl versus Th2 cells to induction of anergy and apoptosis by ECDI/antigen-coupled antigen-presenting cells. Int Immunol 1999; 12:1:57 - 66.
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