Expression of the C-C chemokine receptor 5 in human kidney diseases

Cutaneous T-cell lymphoma (CTCL) is characterized by recruitment of malignant T-cell clones into the skin. The mechanisms involved in tumor homing are still not fully elucidated, though chemokines and chemokine receptors have been suggested to play a role in the pathogenesis. Here, we demonstrate extensive expression of CCR10 in skin biopsies of patients with Sézary syndrome (SS, n = 3), mycosis fungoides (MF, n = 2) and unspecified CTCL (n = 3). In addition, we expand prior findings of CXCR3 expression in MF to other entities of CTCL. Expression of CCR5 was detected in 2 of the examined skin biopsies. The functionality of CCR10 and CXCR3 in SS was demonstrated using the SS T-cell line HUT78. Our data support a potential role of CXCR3 in CTCL and strongly suggest that CCR10 and its ligand CCL27 may contribute to the skin infiltration of malignant T-cells in this group of lymphoproliferative disorders. ' 2005 Wiley-Liss, Inc.

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“…23 Antibody was diluted in PBS. Cells (2 Â 10 6 /reaction) were stained at 48C using a 2-step protocol with FITC-labeled secondary antibody.…”

Section: Flow Cytometrymentioning

confidence: 99%

CCR10 is expressed in cutaneous T‐cell lymphoma

Notohamiprodjo

Segerer

Huss

et al. 2005

Intl Journal of Cancer

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“…Many of the infiltrating T cells potentially recognize autoantigens and therefore perpetuate the disease process. In chronic glomerulonephritis, interstitial nephritis, and transplant rejection, CCR5-positive T cells are abundantly present in areas of interstitial infiltration and their number correlates with the degree of renal insufficiency (6). Apart from T cells, CCR5 is expressed by the majority of monocytes/macrophages within the inflamed tissue.…”

Section: Discussionmentioning

confidence: 99%

“…In a variety of chronic inflammatory diseases, an impressive accumulation of CCR5-positive T cells and macrophages is found at the site of inflammation. An accumulation of CCR5 ϩ cells has been demonstrated in several types of arthritis (4,5), inflammatory renal diseases including transplant rejection (6,7), multiple sclerosis (8,9), and inflammatory bowel diseases (10). In contrast, in the peripheral blood of these patients only a minority of T cells and monocytes express CCR5.…”

mentioning

confidence: 99%

Depletion of CCR5-Expressing Cells with Bispecific Antibodies and Chemokine Toxins: A New Strategy in the Treatment of Chronic Inflammatory Diseases and HIV

Brühl¹,

Cihak

Stangassinger

et al. 2001

The Journal of Immunology

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The chemokine receptor CCR5 is expressed on the majority of T cells and monocytes in the inflammatory infiltrate of diseases such as rheumatoid arthritis, renal diseases, and multiple sclerosis. In contrast, little expression of CCR5 is found on peripheral blood leukocytes. A specific depletion of CCR5+ cells could therefore be a useful strategy to reduce the cellular infiltrate in chronic inflammations. Moreover, CCR5 is the major coreceptor for M-tropic HIV-1 strains. Depletion of CCR5+ leukocytes may help to eliminate cells latently infected with HIV-1. We designed two constructs that specifically destroy chemokine receptor-positive cells. The first construct, a bispecific Ab, binds simultaneously to CCR5 and CD3. Thereby it redirects CD3+ T cells against CCR5+ target cells. The Ab specifically depletes CCR5+ T cells and monocytes, but is inactive against cells that do not express CCR5. Furthermore, ex vivo the bispecific Ab eliminated >95% of CCR5+ monocytes and T cells from the synovial fluid of patients with arthritis. Also, we designed a fusion protein of the chemokine RANTES and a truncated version of Pseudomonas exotoxin A. The fusion protein binds to CCR5 and down-modulates the receptor from the cell surface. The chemokine toxin completely destroyed CCR5+ Chinese hamster ovary cells at a concentration of 10 nM, whereas no cytotoxic effect was detectable against CCR5− Chinese hamster ovary cells. Both constructs efficiently deplete CCR5-positive cells, appear as useful agents in the treatment of chronic inflammatory diseases, and may help to eradicate HIV-1 by increasing the turnover of latently infected cells.

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“…Em estudo anterior, este mesmo grupo de pesquisadores já havia demonstrado que IP-10/CXCL10 (que se liga ao receptor CXCR3), MIP-1a/CCL3 e MIP-1b/CCL4 (que se ligam ao receptor CCR5) estavam aumentados em biópsias renais durante RA. 26 Células inflamatórias infiltrativas, especialmente as células T e os macrófagos, expressaram os receptores de quimocinas, CCR5 e CXCR3. 26 Outro estudo demonstrou, em biópsias de 16 pacientes transplantados, maior expressão de MIG/ CXCL9, CXCR3 e IP-10/CXCL10 naqueles com IF/ TA e glomerulopatia do transplante, com relação àqueles somente com IF/TA.…”

Section: Citocinas E Quimiocinas No Tecido Renal E No Sangue De Transunclassified

“…26 Células inflamatórias infiltrativas, especialmente as células T e os macrófagos, expressaram os receptores de quimocinas, CCR5 e CXCR3. 26 Outro estudo demonstrou, em biópsias de 16 pacientes transplantados, maior expressão de MIG/ CXCL9, CXCR3 e IP-10/CXCL10 naqueles com IF/ TA e glomerulopatia do transplante, com relação àqueles somente com IF/TA. 27 A medida dos níveis plasmáticos pré-transplante destas citocinas e quimiocinas pode ser capaz de predizer a evolução para IF/TA e RA.…”

Section: Citocinas E Quimiocinas No Tecido Renal E No Sangue De Transunclassified