title: Functional analysis of alloreactive memory CD4+ T cells derived from skin transplantation recipient and naïve CD4+ T cells derived from untreated mice.
abstract: BACKGROUND
  Memory T cells (T(M)s) exhibit differential susceptibility to many immunomodulatory strategies that induce immunologic tolerance in naïve T cells, which are believed to be an important barrier to inhibiting rejection and inducing tolerance. As skin grafts are a common model for acquiring T(M)s, we evaluated function of T(M)s derived from skin grafts. We also assessed the modulatory effects on memory T cells function of the microRNAs miR-155 and miR-181a, which are involved in regulating cytokine secretion and TCR sensitivity to antigen, respectively.
  
  
  METHODS
  Memory CD4(+) T cells derived from skin-graft recipient mice, and naïve CD4(+) T cells from untreated mice, were isolated by negative magnetic selection, and then stimulated with dendritic cells pulsed with donor-specific antigens. Effector function and regulating mechanisms were assessed.
  
  
  RESULTS
  In contrast to naïve CD4(+) T cells, CD4(+) T(M)s stimulated with donor-specific antigen could quickly generate effector function in terms of proliferation and cytokine secretion; miR-155 and miR-181a levels in CD4(+) T(M)s rapidly increased during immune response compared to naïve CD4(+) T cells.
  
  
  CONCLUSIONS
  Memory CD4(+) T cells derived from skin grafts could be used as an experimental tool for evaluating effects of different immune-modulating strategies on T(M)s. Levels of miR-155 and miR-181a up-regulated quickly in T(M)s, which could be an important mechanism by which T(M)s mediate immune responses rapidly.
authors.affiliation: Key Laboratory of Transplant Engineering and Immunology, Health Ministry of China, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.forename: Chengwen
authors.initials: C
authors.lastname: Li
authors.forename: Wenqiao
authors.initials: W
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Yanni
authors.initials: Y
authors.lastname: Zhou
authors.forename: Juan
authors.initials: J
authors.lastname: Shan
authors.forename: Shengfu
authors.initials: S
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.forename: Yingjia
authors.initials: Y
authors.lastname: Guo
authors.forename: Youping
authors.initials: Y
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Feng
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology; D023421:Models, Animal; D016038:Skin Transplantation / Q000276:immunology*
chemical_list: C556062:IL10 protein, mouse; D007519:Isoantigens; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; C529100:mirn181 microRNA, mouse; D016753:Interleukin-10; D007371:Interferon-gamma