Anti-lymphocyte function-associated antigen-1 monoclonal antibody inhibits CD40 ligand-independent immune responses and prevents chronic vasculopathy in CD40 ligand-deficient mice1

@article{Corbascio2002AntilymphocyteFA,
  title={Anti-lymphocyte function-associated antigen-1 monoclonal antibody inhibits CD40 ligand-independent immune responses and prevents chronic vasculopathy in CD40 ligand-deficient mice1},
  author={Matthias Corbascio and Harish D. Mahanty and Cecilia {\"O}sterholm and Zhongquan Qi and Thomas C. Pearson and Christian P. Larsen and Chris E. Freise and Henrik Ekberg},
  journal={Transplantation},
  year={2002},
  volume={74},
  pages={35-41}
}
Background. Blockade of CD40 ligand (CD40L; CD154, gp39) is a potential treatment for autoimmune disease and allograft rejection. However, CD40L−/− mice are capable of mobilizing cellular immune responses to viral, parasitic, and intracellular bacterial infections as well as rejecting skin grafts with nearly the same efficiency as wild-type mice. CD40L-deficient mice (CD40L−/−) or wild-type mice treated with anti-CD40L develop chronic vasculopathy only 8 weeks after allogeneic heart… 
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References

SHOWING 1-10 OF 27 REFERENCES
CD40 Ligand Is Not Essential for Induction of Type 1 Cytokine Responses or Protective Immunity after Primary or Secondary Infection With Histoplasma capsulatum
TLDR
The induction of type 1 immune responses (interleukin [IL]-12, interferon [IFN]-γ) has been shown to be important in mediating protection against many intracellular infections including Histoplasma capsulatum and a critical role for CD40 ligand in response to infection is shown.
CD40-gp39 interactions play a critical role during allograft rejection. Suppression of allograft rejection by blockade of the CD40-gp39 pathway.
TLDR
The data suggest that blockade of CD40-gp39 interactions may inhibit allograft rejection primarily by interfering with T cell help for effector functions, rather than by interference with Tcell activation.
Treatment of Allograft Recipients with Donor-Specific Transfusion and Anti-CD154 Antibody Leads to Deletion of Alloreactive CD8+ T Cells and Prolonged Graft Survival in a CTLA4-Dependent Manner1
TLDR
It is concluded that, in the presence of anti-CD154 mAb, DST leads to an allotolerant state, in part by deleting alloreactive transgenic CD8+ T cells, and proposed a unifying mechanism to explain allograft prolongation by DST and blockade of costimulation.
CD40 and CD154 in cell-mediated immunity.
TLDR
The role of the CD40-CD154 system is focused on in the regulation of many newly discovered functions important in inflammation and cell-mediated immunity.
Critical Role for IL-4 in the Development of Transplant Arteriosclerosis in the Absence of CD40-CD154 Costimulation1
TLDR
Elevated intragraft IL-4 production results in an eosinophil infiltrate and is an important mechanism for CD8+ T cell-independent transplant arteriosclerosis in the absence of CD40-CD154 costimulation.
CD40-CD40 Ligand-Independent Activation of CD8+ T Cells Can Trigger Allograft Rejection1
TLDR
It is concluded that CD40L is not an important costimulatory molecule for CD8+ T cell activation and that following transplantation donor APC can activate recipient CD8- T cells directly without first being primed by CD4+ T cells.
Antibody-induced transplant arteriosclerosis is prevented by graft expression of anti-oxidant and anti-apoptotic genes
TLDR
A role for protective genes in the prevention of chronic rejection is shown, and new approaches to protect grafts against development of transplant arteriosclerosis are indicated.
Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways
TLDR
It is reported that simultaneous but not independent blockade of the CD28 and CD40 pathways effectively aborts T-cell clonal expansion in vitro and in vivo, promotes long-term survival of fully allogeneic skin grafts, and inhibits the development of chronic vascular rejection of primarily vascularized cardiac allografts.
Asialo GM1(+) CD8(+) T cells play a critical role in costimulation blockade-resistant allograft rejection.
TLDR
It is demonstrated for the first time that combined blockade of the CD40 and CD28 pathways does not adequately inhibit CD8-mediated skin allograft rejection and evidence is provided that asialo GM1 is a potentially important therapeutic target forCD8-dependent immune responses.
CD8+ T Cells Mediate CD40-independent Maturation of Dendritic Cells In Vivo
TLDR
Antiviral CD8+ T cells are sufficient for the maturation of DCs in the absence of CD40, demonstrating that CD40 is neither involved in Th-dependent nor Th-independent antiviral CTL responses.
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