摘要:

Abstract:A panel of 127 monoclonal antibodies against canine leukocyte antigens, including controls, was distributed to 29 laboratories that performed a variety of experiments to identify groups of antibodies against the canine equivalents of some of the human CD antigens. Cluster analysis was performed centrally, using the submitted antibody binding data from immunofluorescence, ELISA and immuno‐histology experiments. Immunoprecipitation for molecular weight determination was also performed centrally with T‐cell blasts and a B‐cell line as the sources of antigen. Clusters of three or more antibodies were found that defined the canine equivalents of the CD5, CD4, CD8 and Thy‐1 antigens, and these could be used to label T‐cell subsets from the peripheral blood. Other groups of monoclonal antibodies recognized the canine homologues of the CD11/18 group of antigens, CD44 and the CD45/CD45R antigen family: these should be useful in isolating functional subsets of CD4+helper T cells. There was a cluster of four antibodies that bound strongly to platelets (probably CD41 antigen), three antibodies that were specific to B cells (including CD21) and two antibodies against a granulocyte antigen (possibly CD15). A number of reagents were found against canine MHC‐II and immunoglobulin, with some of the latter able to distinguish between Ig subclasses. Properties of each of the canine antigens defined by these monoclonal antibodies are discussed and compared with other species. The availability of such a panel of reagents should allow rapid improvements in the immunological diagnosis of canine disease, and there might now be a potential for testing novel therapeutic strategies in a clinical veterin

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02315.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:A state of tolerance to MHC mismatched allografts can be generated in rodents by treatment with CD4 and CD8 monoclonal antibodies (mAb). In order to transpose this type of therapy to large animals and ultimately to the clinic, a suitable model is required. To this end we have generated a series of mAb to the canine CD4, CD8, and Thy‐1 antigens and have tested their ability to prevent rejection of renal allografts. Donor‐recipient pairs were selected from a colony of mongrel dogs in which untreated rejection of two haplotype‐mismatched kidneys occurred by day 7 (defined as a serum creatinine>300 μmol/l). Therapy with either the CD4 or the CD8 mAb, using no other immunosuppression, did not prolong graft survival. Depletion of T cells by a Thy‐1 mAb prior to surgery only extended graft survival to day 9. However, treating with combinations of mAb up to day 10 (CD4 plus Thy‐1; CD4 plus CD8; or CD4 plus CD8 plus Thy‐1) prolonged renal allograft function up to 25 days. Combination of the triple mAb therapy with a sub‐therapeutic immunosuppressive drug regimen (cyclosporin A plus azathioprine that alone gave a median survival of 15 days) favored survival to a median of 38 days. This protocol also inhibited the antiglobulin response that had curtailed the effects of mAb treatment, opening the way to more extended, and potentially tolerizing, mAb plus

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02316.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:Two murine monoclonal antibodies specific for IFN‐γ, ADI‐1, and ADI‐23 (both IgG1 kappa), were generated in BALB/c mice. The ADI‐1 exhibited a higher avidity for canine rIFN‐γ than for nIFN‐γ and human rIFN‐γ. In contrast, the ADI‐23 showed equal avidity for the three IFN‐γ preparations. The anti‐canine IFN‐γ mAb did not bind to mouse and rat rIFN‐γ. The ADI‐1, and ADI‐23 mAb were also tested for binding to human rTFN‐α and, contrary to our expectations, it was found that ADI‐23 showed significant binding to human rTFN‐α and rIFN‐γ, in contrast to ADI‐1. Both anti‐canine IFN‐γ mAb stained 48‐h PHA‐induced dog lymphoblasts. A two‐site mAb ELISA was developed, which was linear in the range of 7–500 ng of canine rIFN‐γ, which indicated that the two mAb detected non‐overlapping epitopes on the canine rIFN‐γ molecule. We studied the effect of ADI‐1 on the prolongation of canine renal allografts. Recipients of kidney allografts, that were treated with ADI‐1 by continuous arterial infusion, were prolonged to 22 and 25 da

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02317.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Abstract:Prevention of graft‐versus‐host disease by depletion of CD6‐positive T cells was studied in the dog. Donors were DLA‐homozygous, recipients DLA‐heterozygous with one DLA haplotype identical to the donor. Seven control dogs received untreated marrow and died of GvHD after full hemopoietic recovery within 28 days of transplantation. For prevention of GvHD, immunomagnetic separation of T cells with a monoclonal antibody against human CD6 that crossreacted with canine T cells was evaluated. Depletion of CD6‐positive cells depleted CD4‐positive cells completely, but only part of CD8‐positive cells and DR‐positive cells. CD6‐depleted marrow exhibited strong nonspecific “natural” suppression of the generation of cytotoxic T cellsin vitro.Eleven dogs received CD6‐depleted marrow. Only 1 dog developed GvHD and died. Sustained engraftment was seen in 8 dogs. Hemopoietic recovery was delayed and slower after transplantation of CD6‐depleted marrow than after transplantation of untreated marrow. Four of these dogs were treated with G‐CSF, and this accelerated the recovery of leukocytes, but did not prevent rejection. Chimerism was mixed in 7 of 10 evaluable dogs and 1 dog recovered its own hemopoiesis 2 years after transplantation. CD6 depletion prevents GvHD across a DLA‐haplotype difference, but rejection and mixed chimerism may occur. Treatment with G‐CSF accelerates leukocyte recov

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02318.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02319.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02320.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02321.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02322.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02323.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0001-2815    

DOI:10.1111/j.1399-0039.1994.tb02324.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY