title: Inactivation of T-cell receptor-mediated integrin activation prolongs allograft survival in ADAP-deficient mice.
abstract: BACKGROUND
  Signaling through the T cell receptor (TCR) leads to profound changes in the function and properties of T cells, including integrin activation. Adhesion and degranulation promoting adapter protein (ADAP) is an adapter protein linking T cell receptor stimulation to integrin activation. We aim to clarify how disruption of TCR-mediated integrin activation affects alloreactive immune responses.
  
  
  METHODS
  In vitro T cell proliferation and the cytokine production was determined. In vivo cytotoxic T lymphocyte (CTL) activity was measured as well. Allogenic skin and heart transplantation was used to test the in vivo role of ADAP in alloimmune responses. Histology and flow cytometry was applied to analyze the graft infiltrating lymphocytes.
  
  
  RESULTS
  Upon stimulation with allogenic dendritic cells ADAP-deficient T cells displayed impaired proliferative responses compared to wild type (WT) T cells. This was accompanied by significantly decreased production of the cytokine interleukin-2. In contrast, the in vivo CTL activity in ADAP-deficient mice was comparable to that of WT mice. Consistently, we observed a prolongation of fully major histocompatibility complex (MHC)-mismatched heart transplants in ADAP deficient mice. Protection of allogenic heart grafts in ADAP-deficient mice was accompanied by a decrease in the infiltration, proliferation and activation of T cells in the allograft. However, no effect was observed after fully MHC-mismatched skin transplantation.
  
  
  CONCLUSIONS
  We have shown that although ADAP is dispensable for the rejection of allografts, ADAP function plays an important role for the efficacy of graft rejection. ADAP's main function appears to affect the induction phase of the immune response.
authors: Kidney Disease Center, The 1st Affiliated Hospital of Zhejiang University, Zhejiang, China.
authors: Jiong
authors: J
authors: Tian
authors: Oliver
authors: O
authors: Pabst
authors: Dorothee
authors: D
authors: Römermann
authors: Susanne
authors: S
authors: Skubich
authors: Reinhold
authors: R
authors: Förster
authors: Jan
authors: J
authors: Beckmann
authors: Jiang-Hua
authors: JH
authors: Chen
authors: Matthias W
authors: MW
authors: Hoffmann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology / Q000502:physiology; D049109:Cell Proliferation; D006085:Graft Survival / Q000502:physiology*; D016027:Heart Transplantation / Q000473:pathology / Q000502:physiology*; D016023:Integrins / Q000502:physiology*; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016038:Skin Transplantation / Q000473:pathology / Q000502:physiology*; D014184:Transplantation, Homologous
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491468:Fyb protein, mouse; D016023:Integrins; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell