Biomedical subjects

A C Avery

Publications and source records attributed to A C Avery.

6 recordsLinked to original sources

PubMed2006

Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs with cancer.

Regulatory T cells (Treg) are a distinct group of T lymphocytes with immunosuppressive properties that serve normally to prevent harmful autoimmune responses. However, Tregs can also interfere with beneficial immune responses such as anti-tumor and anti-viral immunity in humans and rodents. Given the overall importance of Tregs, it is likely that they play an important role in diseases of dogs as well. However, at present reagents required for identification of Tregs in dogs are not available. Therefore, we investigated whether expression of FoxP3, a transcription factor that is highly expressed in Tregs in humans and rodents could also be used to identify Tregs in dogs. We found that a cross-reactive FoxP3 antibody identified a subset of CD4(+) T cells in blood and lymph nodes of dogs. By flow cytometry the mean percentage of FoxP3(+)CD4(+) T cells in normal dogs was 4.3% in blood and 9.8% in the lymph nodes. In dogs with cancer, there was a significant increase in numbers of Treg in blood (7.5%) and tumor-draining lymph nodes (17.1%) compared to age-matched healthy control dogs. We also found that FoxP3(+)CD4(+) T cells in dogs could be significantly expanded in vitro by TCR activation together with addition of TGF-beta and IL-2. Treated cells also significantly increased expression of TGF-beta and IL-10mRNA. We conclude from these studies that a cross-reactive FoxP3 antibody can be used to identify Tregs in dogs and that this reagent may serve as a useful tool for investigating the role of Treg in a variety of diseases of dogs.

Animals↗

PubMed2003

Diagnosis of canine lymphoid neoplasia using clonal rearrangements of antigen receptor genes.

Although the diagnosis of canine leukemia and lymphoma in advanced stages is usually uncomplicated, some presentations of the disease can be a diagnostic challenge. In certain situations, lymphoma and leukemia can be difficult to distinguish from a benign reactive proliferation of lymphocytes. Because clonality is the hallmark of malignancy, we have developed an assay that uses the polymerase chain reaction to amplify the variable regions of immunoglobulin genes and T-cell receptor genes to detect the presence of a clonal lymphocyte population. The assay detected clonally rearranged antigen receptor genes in 91% of the 77 dogs with lymphoid malignancy. Of the 24 dogs tested, that were either healthy or had clearly defined conditions not related to lymphoid malignancy, a clonally rearranged antigen receptor gene was found in one (a dog with Ehrlichia canis infection). Gene rearrangement was appropriate for the immunophenotype (immunoglobulin gene rearrangement in B-cell leukemias and T-cell receptor gene rearrangement in T-cell leukemias). Dilution analysis showed that the clonal rearrangement could be detected when 0.1-10% of the DNA was derived from neoplastic cells, depending on the source tissue. Potential applications of this assay include the diagnosis of lymphoma or leukemia in biopsy samples, cavity fluids, fine needle aspirates, bone marrow and peripheral blood; the determination of lineage (B or T cell); staging of lymphoma; and detection of residual disease after chemotherapy.

Animals↗

PubMed1997

Plasmodium yoelii: resistance to disease is linked to the mtv-7 locus in BALB/c mice.

We have identified congenic mouse strains that differ dramatically in resistance to infection with the murine malaria parasite Plasmodium yoelii 17X. After infection, BALB/c mice develop severe anemia and a high degree of parasitemia which sometimes results in death. The mtv-7 congenic strain BALB.D2.mlsa, however, develops only a mild degree of anemia and parasitemia. In this paper we describe the course of the disease and discuss the potential role of mtv-7 and linked loci in control of this infection. These mice differ in their response to anemia, which may contribute to their differential susceptibility to disease; however, no influence of mtv-7 reactive T cells was documented.

Anemia↗

PubMed1995

Resistance to herpes stromal keratitis conferred by an IgG2a-derived peptide.

Not all peripheral tissue antigens enter the thymus and it is unclear how the immune system remains tolerant to this class of self antigen. As tolerance to self peptides can generate gaps in the T-cell repertoire for cross-reactive foreign antigens, we investigated whether this mechanism might also diminish autoimmune reactions to similar peptides expressed by peripheral tissues. Herpes stromal keratitis (HSK) is a virally induced autoimmune reaction against corneal tissues mediated by T cells, and is a leading cause of human blindness. Resistance to HSK in mice is associated with allotypic variation in immunoglobulin genes, possibly because circulating immunoglobin-derived peptides can cross-tolerize T cells specific for corneal tissue autoantigens. Here we show that HSK is mediated by T-cell clones specific for corneal self antigens which also recognize an allotype-bearing peptide derived from IgG2a, and that exposure of HSK-susceptible mice to a soluble form of this peptide confers resistance to HSK. Shared expression of peptide subsequences between sequestered tissue proteins and circulating proteins may be important for maintenance of self-tolerance and prevention of autoimmunity.

Animals↗

PubMed1994

Activation of T cells by superantigen in class II-negative mice.

The ability of the staphylococcal enterotoxins to stimulate T cells has been thought to depend on their association with class II MHC products. Here, we demonstrate that a subgroup of staphylococcal enterotoxins, which includes staphylococcal enterotoxin C and staphylococcal enterotoxin E, stimulates strong MHC-independent responses, thereby resulting in T cell expansion and generation of CTL. The immunologic consequences of MHC-independent activation of T cells by superantigens differ from those of class II-dependent activation, inasmuch as this pathway does not result in detectable T cell deletion. These findings delineate a novel MHC-independent T cell activation pathway that leads to both clonal expansion and expression of CTL effector function in response to a subgroup of bacterial superantigens.

Animals↗

PubMed1972

Food service.

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Computers↗