title: Differential susceptibility of naïve versus cloned CD4+ T cells to antigen-specific and MHC-restricted anergy induction.
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 naïve 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 homogeneous 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 naïve 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 naïve CD4(+) transgenic T cells under the same conditions. The results suggest that naïve 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.
authors.affiliation: Department of Immunology of Shanghai Medical College of Fudan University, Key Laboratory of Molecular Medicine of Ministry of Education, Shanghai Gene Immunization Vaccine Research Center, Shanghai 200032.
authors.forename: Quan-Sheng
authors.initials: QS
authors.lastname: Liu
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: Zhang
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Chu
authors.forename: Si-Dong
authors.initials: SD
authors.lastname: Xiong
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D017635:Clonal Anergy / Q000235:genetics / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis; D007108:Immune Tolerance / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell