Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence‐based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause severe reproductive and respiratory pathologies resulting in immense monetary and welfare costs for the swine industry. The vaccines against PRRSV are available; but they struggle with providing protection against the plethora of heterologous PRRSV strains. To improve PRRSV vaccine development, the aim of this study was to provide an in-depth analysis of the crucial heterologous T-cell response to type-2 PRRSV. Following PRRSV modified live virus (MLV) vaccination or infection using one high- or one low-pathogenic PRRSV-strain, this nine-week study evaluated the T-cell response to different PRRSV strains. Our results demonstrate an important role for T cells in this homo- and heterologous response. Specifically, the T-helper cells were the main responders during viremia. Their peak response at 28 dpi correlated with a reduction in viremia, and their homing receptor expression indicated the additional importance for the anti-PRRSV response in the lymphatic and lung tissue. The cytotoxic T lymphocyte (CTL) response was the strongest at the site of infection—the lung and bronchoalveolar lavage. The TCR-γδ T cells were the main responders post viremia and PRRSV induced their expression of the lymph node homing the chemokine receptor, CCR7: This indicates a crucial role for TCR-γδ T cells in the anti-PRRSV response in the lymphatic system.
HIV-induced AIDS may be mediated by the activation of immunosuppressive CD4+CD25+ T regulatory cells (Treg cells). Treg cells have been shown to regulate CD4+ and CD8+ immune responses to HIV and FIV antigens in vitro. We tested the hypothesis that Treg cells become infected and activated during the acute infection with FIV leading to the suppression of CD4+ T helper cell responses. Cats were experimentally infected with FIV-NCSU1 and blood and lymph node cells were collected at weekly intervals following inoculation. Real-Time RT-PCR was used to determine plasma viremia and the relative expression of FIV, FoxP3, TGF-β, and GAPDH mRNA copies in CD4+CD25+ and CD4+CD25− T cell subsets. Flow cytometry was used to assess the absolute numbers of each cell type and the expression of surface TGF-β and intracellular FoxP3 in CD4+CD25+ and CD4+CD25− T cells at each time point. Treg suppression of IL-2 production in CD4+ T helper cells was assessed by ELISPOT assays. Our results showed that peak viremia occurred at 2 weeks post infection and correlated with maximal infectivity in CD4+CD25+ T cell populations. FIV-gag-mRNA levels were higher in CD4+CD25+ T cells than CD4+CD25− T cells throughout the acute phase of infection. Induction of FoxP3 and TGF-β indicated activation of Treg cells during the acute stage infection, which was confirmed by Treg cell suppression of IL-2 production by CD4+ Th cells in an ELISPOT assay. Our findings support the hypothesis that early activation of Treg immunosuppressor function may limit an effective anti-FIV response, contributing to the establishment of chronic infection and the immunodeficiency caused by this virus.
Background: Immunohistochemistry (IHC), flow cytometry (FC), and PCR for antigen receptor rearrangements (PARR) are 3 widely utilized tests to determine immunophenotype in dogs with lymphoma (LSA).Objectives: This study evaluated the ability of FC and PARR to correctly predict immunophenotype as defined by IHC and to determine the level of agreement among the 3 tests.Animals: Sixty-two dogs with lymphoma. Methods: Retrospective study. Medical records were searched to identify dogs with LSA that had concurrent IHC, FC, and PARR performed. Immunophenotype results were categorized as B-cell, T-cell, dual immunophenotype (B-and T-cell), or indeterminate. The results of FC and PARR were evaluated for correctly classifying B-and T-cell LSA as compared with IHC. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated in addition to concordance between each test.Results: The sensitivity of FC was significantly higher than PARR for both B-cell (91% versus 67%; P < 0.0072) and T-cell (100% versus 75%; P < 0.0312) LSA. The percent agreement between FC and IHC was 94%, between PARR and IHC was 69%, between FC and PARR was 63%, and among all 3 tests was 63%.Conclusions and Clinical Importance: Flow cytometry is superior to PARR in correctly predicting immunophenotype when evaluating lymph nodes from dogs already diagnosed with B-or T-cell LSA. If fresh samples are not available for FC, PARR is an acceptable assay for determination of immunophenotype given its high specificity.
CD8þ lymphocytes are critical to the control and elimination of viral pathogens. Impaired CD8 þ responses are well recognized in lentiviral infections; however, the mechanisms underlying CD8 þ impairment remain elusive. Using the feline immunodeficiency virus (FIV) model for human AIDS, we reported previously that CD4 þ CD25 þ Treg cells in both the acute and long-term, asymptomatic phase of infection are constitutively activated and suppress CD4 þ CD25-T cell responses. In the current study, we have demonstrated that CD4 þ CD25 þ Treg cells suppress CD8 þ responses to immune stimulation during both the acute and chronic, asymptomatic phase of FIV infection and that the mechanism of suppression may be mediated by membrane-þ lymphocytes from lymph node suspensions significantly enhanced production of IFN-g during the acute phase of infection and coculture of CD8 þ lymphocytes with CD4 þ CD25 þ lymphocytes resulted in suppression of CD8 þ IFN-g during both the acute and chronic stages of infection. FACS analysis indicated that there was TGF-bRII upregulation on CD8 CD25þ subset in chronically infected cats. In support of activation of the TGF-b signaling pathway, Western blotting showed Smad 2 phosphorylation in CD8coculture. These results demonstrate the suppressive effect CD4 þ CD25 þ Treg cells have on the CD8 þ immune response during the acute and chronic stages of FIV infection and suggest that the mechanism of suppression may be mediated by mTGF-b.
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