ABSTRACT
PURPOSE: The primary objective of the present study was to identify the kinetics and origin of ocular infiltrating T cells in a preclinical model of graft-versus-host disease (GVHD) that induces eye tissue damage. METHODS: Graft-versus-host disease was induced using an major histocompatibility complex (MHC)-matched, minor histocompatibility-mismatched hematopoietic stem cell transplant (HSCT) model. This approach, which utilized congenic and EGFP-labeled donor populations, mimics a matched, clinically unrelated donor (MUD) cell transplant. Systemic and ocular GVHD were assessed at varying time points using clinical examination, intravital microscopy, immune phenotype via flow cytometric analyses, and immunohistochemical staining. RESULTS: Following transplant, we observed characteristic changes in GVHD-associated immune phenotype as well as clinical signs present in recipients post transplant. Notably, the kinetics of the systemic changes and the ocular damage paralleled what is observed clinically, including damage to the cornea as well as the conjunctiva and lacrimal gland. Importantly, the infiltrate contained predominantly donor CD4 as well as CD8 T cells with an activated phenotype and macrophages together with effector cytokines consistent with the presence of a TH1 alloreactive population. CONCLUSIONS: Overall, the findings here unequivocally demonstrated that donor T cells compose part of the corneal and ocular adnexa infiltrate in animals undergoing ocular GVHD. In total, the results describe a novel and promising preclinical model characterized by both systemic and ocular changes as detected in significant numbers of patients undergoing GVHD following allo-HSCT, which can help facilitate dissecting the underlying immune mechanisms leading to damage associated with ocular GVHD.
Subject(s)
Eye Diseases/therapy , Graft vs Host Disease/therapy , Hematopoietic Stem Cell Transplantation , T-Lymphocytes/transplantation , Animals , Disease Models, Animal , Eye Diseases/immunology , Eye Diseases/pathology , Graft vs Host Disease/immunology , Graft vs Host Disease/pathology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Transplantation, HomologousABSTRACT
<p><b>OBJECTIVE</b>To study the relationship between soluble resistance-related calcium-binding protein (sorcin) gene and multidrug resistance gene (mdr1), and their significance in clinical drug resistance and prognosis of acute myeloid leukemia (AML).</p><p><b>METHODS</b>Amplification of sorcin gene and mdr1 gene in K562/A02 cell detected by Northern blot, were monitored by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) in 65 AML patients and 27 normal controls, with their relationship and clinical outcame analyzed.</p><p><b>RESULTS</b>The amplification of sorcin gene and mdr1 gene in AML patients were significantly higher than that in the normal control, which were related to clinical drug resistance and prognosis. The amplification of sorcin gene was related to the amplification of mdr1 gene in the two groups. The clinical drug resistance incidence rate and complete remission rate were 92.9% and 7.1% in sorcin(+)/mdr1(+) group. They were 8.6% and 91.4% in the sorcin(-)/mdr1(-) group (P < 0.001).</p><p><b>CONCLUSION</b>The co-amplification of sorcin and mdr1 gene can be taken as a good indicator of clinical drug resistance and prognosis of AML.</p>
Subject(s)
Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Genetics , Acute Disease , Blotting, Northern , Methods , Calcium-Binding Proteins , Genetics , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Gene Expression , K562 Cells , Leukemia, Myeloid , Genetics , Neoplasm Proteins , Genetics , PrognosisABSTRACT
<p><b>OBJECTIVE</b>To study the relationship between the expression of soluble drug resistance-related calcium-binding protein (sorcin) gene and the clinical multidrug resistance in acute leukemia (AL).</p><p><b>METHODS</b>A semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate the transcription levels of the human sorcin gene in 95 AL patients and 27 controls.</p><p><b>RESULTS</b>Sorcin gene expression was significantly higher in AL patients than in normal contrls (P < 0.001), and higher in relapsed/refractory acute myeloid leukemia (AML) patients than in those newly diagnosed or in complete remission. Sorcin gene overexpression was significantly lower in non-resistant patients than in resistant ones (P < 0.001). CR rates of these two groups were 20.0% and 80.0%, respectively. Sorcin gene expression was higher in AML-M(5) patients than M(2), M(3), M(4) patients.</p><p><b>CONCLUSION</b>Sorcin gene overexpression is significantly associated with clinical multidrug resistance and prognosis, it is one of the indicators for predicting prognosis of AL patients.</p>
