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Cytotoxic Phenotype (cytotoxic + phenotype)
Selected AbstractsPredominant Th1 and Cytotoxic Phenotype in Biopsies from Renal Transplant Recipients with Transplant GlomerulopathyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009S. Homs Transplant glomerulopathy (TGP) appears to be a pathogenic feature of chronic antibody-mediated rejection, but the pathogenesis of this histologic entity is still poorly understood. Previous studies suggest the involvement of lymphocytes but the phenotypes of these cells have never been analyzed. Here, we report the first study of mRNAs for specific markers of CD4+ T cells including Th1 (T-bet and INF,), Th2 (IL4 and GATA3), Treg (Foxp3) and Th17 (IL-17 and ROR,t) subsets, cytotoxic CD8 T cells (Granzyme B) and B-cell markers (CD20) in renal biopsies from renal transplant recipients suffering interstitial fibrosis and tubular atrophy (IF/TA) with or without TGP but with a similar inflammatory score and controls including transplant recipients with normal renal function. Only INF,, T-bet (both functionally defined markers of Th1 CD4 T cells) and granzyme B (a CD8 cytotoxic marker) were significantly more strongly expressed in patients with TGP than in patients without TGP and normal controls. These results indicate a role of an active T-mediated inflammatory and cytotoxic process in the pathogenesis of TGP. [source] CD8-positive juvenile onset mycosis fungoides: an immunohistochemical and genotypic analysis of six casesBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2000L.R. Whittam Background,Childhood cases of cytotoxic T-cell lymphoma have not been well described. Objectives,We have undertaken an immunohistochemical and genotypic analysis of patients presenting with juvenile onset mycosis fungoides (MF). Patients/methods,Of 10 patients presenting over a 3-year period, six exhibited a CD8-positive phenotype. These six patients were also CD2, CD3 and TIA1 positive, but CD56 negative. Apart from the cytotoxic phenotype, these patients had clinicopathological features that were indistinguishable from ordinary cases of MF, with slowly evolving patches and plaques. Three patients were staged as 1A and three as 1B, with no evidence of nodal or systemic disease. Results,Patients responded well to conventional therapy, with no evidence of disease progression after 3 years follow-up. Epidermotropism was a prominent feature in four of the six cytotoxic cases. In two patients with an equivocal histology the diagnosis was confirmed by the finding of a clonal population, using polymerase chain reaction/single strand conformational polymorphism analysis of the T-cell receptor gamma gene in lesional skin. The same technique revealed that all blood samples analysed were polyclonal. Conclusions,These data show that cytotoxic T-cell lymphoma can pursue an indolent course and that cases of CD8-positive MF may be over-represented in childhood. [source] Characterization of bone marrow T cells in monoclonal gammopathy of undetermined significance, multiple myeloma, and plasma cell leukemia demonstrates increased infiltration by cytotoxic/Th1 T cells demonstrating a squed TCR-V, repertoireCANCER, Issue 6 2006Martin Pérez-Andres M.D. Abstract BACKGROUND The majority of studies published to date regarding the role of the bone marrow (BM) microenvironment in the pathogenesis of monoclonal gammopathies (MG) have focused on the interaction between stroma cells and plasma cells, whereas information concerning the lymphocytes infiltrating the tumor microenvironment is scanty. METHODS The authors measured the distribution, TCR-V, repertoire, immunophenotype, and functional characteristics of different subsets of BM T lymphocytes from 61 nontreated patients with MG (30 patients with MG of undetermined significance [MGUS], 27 patients with multiple myeloma [MM], and 4 patients with plasma cell leukemia [PCL]). RESULTS The authors found a significantly increased rate of BM infiltration by T cells in all patient groups, at the expense of CD4+CD8, and CD4,CD8, T lymphocytes and both CD4+CD28, and CD8+CD28, cytotoxic/effector T cell subsets, and associated with TCR-V, expansions in both CD4+ and CD8+ BM T cells in the majority of patients with MGUS, MM, and PCL. Moreover, the percentage of T cells secreting interferon (IFN)-, was found to be increased (P , 0.05) both in CD4+ and CD8+ T cells in MGUS and MM patients, and a higher plasma concentration of IFN-, was found in patients with MM. It is interesting to note that a positive correlation was noted between the proportion of CD28, and both the percentage of IFN-,,secreting cells and the proportion of expanded TCR-V, lymphocytes within the total BM CD4+ T cells. CONCLUSIONS The results of the current study demonstrated an increased infiltration of BM by T cells associated with frequent TCR-V, expansions and a more prominent cytotoxic/Th1 phenotype in all the patient groups studied. Cancer 2006. © 2006 American Cancer Society. [source] Peripheral T-cell lymphoma associated consecutively with hemophagocytic lymphohistiocytosis and hypereosinophilic syndromeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2003Antonio Gutiérrez Abstract:, Both hemophagocytic lymphohistiocytosis and hypereosinophilic syndrome have been associated with hematologic neoplasms and are respectively related to an overproduction of the cytokines Thelper 1 (Th1) and Th2 by tumor cells or reactive cells. To our knowledge, this is the first time a case of a peripheral T-cell lymphoma consecutively associated with both paraneoplastic conditions has been reported. Importantly, in this case when the lymphoma exclusively involved the bone marrow, severe paraneoplastic systemic damage, a CD8+ suppressor/cytotoxic phenotype and a hypereosinophilia not related to high levels of interleukin (IL)-5 was found. Interestingly, progression of the lymphoma coincided with an increase in the serum levels of several Th2 cytokines and IL-2, a decrease in tumor necrosis factor and granulocyte-macrophage colony-stimulating factor levels and the onset of a hypereosinophilic syndrome. [source] |