Canine diabetes mellitus (DM) shares many similarities with human type 1 diabetes (T1D). It is a complex genetic disorder, which shows marked differences in breed susceptibility, with Samoyed dogs being highly susceptible, whereas the Boxer breed is relatively resistant. A number of immune response genes, which have been associated with human T1D, have also been implicated in determining suscep...

To facilitate the establishment of mixed chimerism with limited dose of bone marrow (BM) cells, and to achieve tolerance in skin graft model, combined blocking of costimulatory pathway and IL-2 pathway was used in minimally myeloablative model using busulfan. BM cells (2.5x10(7)) of BALB/c were injected into C57BL/6 mice at day 0 with full thickness skin graft after single dose injection of bus...

The B7-1 molecule, expressed on antigen presenting cells (APC), provides a crucial costimulatory signal for T cell activation. Recent studies demonstrate the existence of alternative, non-B7-1 CTLA4 counter-receptors in mice and humans. Here, we describe the molecular cloning and demonstrate costimulatory function of the murine B7-2 (mB7-2) gene. Murine B7-2 cDNA encodes a member of the Ig supe...

The gene of Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4), a negative regulator of T lymphocytes, contains a single-nucleotide polymorphism (SNP) at position +6230A->G (ct60A->G), which has been found associated with several autoimmune diseases and appears to reduce T-cell inhibitory activity. In Ghana, West Africa, we compared the frequencies of CTLA4 +6230 A/G and 6 haplotype-tagging SN...

The March 2007 issue of Arthritis Research and Therapy included a research article by Gottenberg and colleagues [1] that reports a failure to confirm our previous study [2] of a genetic association between CTLA4 and primary Sjögren's syndrome (pSS). Similar to our study, the Gottenberg study analysed both CTLA4 CT60 and +49A/G single nucleotide polymorphisms (SNPs). They observed an association...

PURPOSE To examine the role of the CD28-CD80-CD86 pathway of T-lymphocyte costimulation in corneal allograft rejection and the effect of blockade of that pathway on graft survival. METHODS Kinetics of CD80 and CD86 expression in the cornea and draining lymph nodes were examined by RT-PCR and immunohistochemistry in untreated allograft recipients in a high-responder rat model. The effect of bl...

CTL-associated antigen 4 (CTLA4) blockade releases inhibitory controls on T cell activation and proliferation, inducing antitumor immunity in both preclinical and early clinical trials. We examined the mechanisms of action of anti-CTLA4 and a GM-CSF-transduced tumor cell vaccine (Gvax) and their impact on the balance of effector T cells (Teffs) and Tregs in an in vivo model of B16/BL6 melanoma....

BACKGROUND Canine pemphigus foliaceus is an autoimmune antibody-mediated skin disease characterized by acantholysis. The objective of this case report is to present the successful management of steroid refractory pemphigus foliaceus with cytotoxic T-lymphocyte antigen 4 (CTLA4)-overexpressing adipose tissue mesenchymal stem cells (ATMSCs). CASE PRESENTATION A 10-year-old, 12.3-kg, castrated m...

Two fully human monoclonal antibodies (mAbs) that target cytotoxic T lymphocyte-associated antigen 4 (CTLA4), tremelimumab and ipilimumab, are in clinical development for the treatment of advanced cancers. The investigational agents enhance T-cell activation and are hypothesized to generate antitumor immunity. Clinical data have shown that treatment with an anti-CTLA4 mAb is tolerable in most p...

Sensitization to donor Ags is an enormous problem in clinical transplantation. In an islet allograft model, presensitization of recipients through donor-specific transfusion (DST) 4 wk before transplantation results in accelerated rejection. We demonstrate that combined DST with anti-CD154 (CD40L) therapy not only prevents the deleterious presensitization produced by pretransplant DST in the is...