Tubulointerstitial lesions, occurring in many kinds of renal diseases, have been found to be the predominant factor in the impairment of renal function. The severe and extensive lesions often predict a poor outcome in...Tubulointerstitial lesions, occurring in many kinds of renal diseases, have been found to be the predominant factor in the impairment of renal function. The severe and extensive lesions often predict a poor outcome in future. It has been tested recent years that the infiltrating inflammatory cells might play important roles in the onset and deterioration of tubulointerstitial injuries. On the other hand, the resident cells, including the tubular epithelial cells and the fibroblasts, also directly take part in tubulointerstitial inflammation and fibrosis. Researches also display implicated interactions between the infiltrating cells and the resident cells, which contribute to the amplification of inflammation and the progress of fibrosis.展开更多
Background: CD4+ and CD8+ T lymphocytes play different roles in the outcome of leishmaniasis. However, T- cell distribution in lesions shows significant variability in in situ immunocytochemical studies. Objectives: I...Background: CD4+ and CD8+ T lymphocytes play different roles in the outcome of leishmaniasis. However, T- cell distribution in lesions shows significant variability in in situ immunocytochemical studies. Objectives: In this report flow cytometry was used to determine the predominant T- cell subsets in leishmaniasis lesions, and their relationship with Leishmania- responsive circulating T cells. Patients and methods: Mononuclear cells from lesions or peripheral blood (PBMC) of 34 cutaneous (CL), four mucosal (ML) and four disseminated leishmaniasis were phenotypically characterized by flow cytometry. Leishmania- responsive T cells were obtained after in vitro stimulation of PBMC with leishmanial antigens. Results/conclusions: Variable amounts of γ δ lymphocytes were present in all lesions, with no association with duration of illness. The highest percentages of interleukin- 2R- and interferon- γ R- positive cells were observed in ML lesions and could render these T cells more susceptible to the effects of these cytokines. The distribution of intralesional T- lymphocyte subsets was quite variable (CD4+ > CD8+ =18 cases, CD8+ >CD4+ =12 cases and CD4+ CD8+ =4 cases) without any association with clinical parameters, and could explain the controversy regarding proportions of these T- cell subsets in leishmaniasis lesions. Low percentages of Leishmania- reactive CD8+ T cells were observed in blood while an enrichment of CD8+ cells was shown in the inflammatory infiltrate, suggesting that local immunoregulatory factors could favour the recruitment and/or proliferation of local CD8+ lymphocytes. Increased percentages of CD8+ cells observed in older lesions are consistent with the hypothesis that they can mediate healing, although their involvement in tissue damage cannot be ruled out. It is possible that these mechanisms can influence the clinical outcome or even the response to therapy.展开更多
Background: There have been only two reports on immunophenotypic characteriza tion in the cutaneous lesions of dermatomyositis (DM) that emphasize the importa nce of the infiltrating CD4+ T lymphocytes. Objectives: To...Background: There have been only two reports on immunophenotypic characteriza tion in the cutaneous lesions of dermatomyositis (DM) that emphasize the importa nce of the infiltrating CD4+ T lymphocytes. Objectives: To characterize the imm unophenotype of the cells that infiltrate the lesional skin of DM and to evaluat e the possible T-helper (Th) polarization Th1/Th2 through detection of specifi c cytokines, chemokine receptors and markers of cellular activation. Methods: Sk in biopsy specimens derived from pathognomonic lesions (Gottron’s papules and Gottron’s sign) of eight patients withDMwere immunostainedwith a large panel o fmonoclonal antibodies to CD3, CD4, CD8, myeloperoxidase(MPO), eosinophil cation ic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR, interleukin (IL)- 2, IL- 4, IL- 5, IL- 13, interferon-γ , tumour necrosis factor-α , recept or 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines, using the alka line phosphatase-antialkaline phosphatase method. Control specimens were obtai ned from five healthy subjects and from six patients with discoid lupus erythema tosus. Results: Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+ ) were the principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was a pproximately 2· 5. A mixed Th1/Th2 profile and higher Th1 cytokine production t ogether with significant staining for CXCR3 were detected. Neutrophil granulocyt es were the second most abundant population; eosinophil granulocytes were very p oorly represented. Conclusions: Activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction betw een CD40 andCD40L could be an important mecha nismof cellular activation in cutaneous immune-mediated inflammation by ind uction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. T here was a significant quantity of MPO+ cells (neutrophil granulocytes) in the in-flamed tissue, and they might have a role in sustaining the chronic inflam mation.展开更多
Background: Current evidence suggests that lichen planus is a T-cell-mediated autoimmune disease in which cytotoxic mechanisms have been poorly investigated. Objectives: We investigated the expression of perforin in s...Background: Current evidence suggests that lichen planus is a T-cell-mediated autoimmune disease in which cytotoxic mechanisms have been poorly investigated. Objectives: We investigated the expression of perforin in subpopulations of peripheral blood lymphocytes(PBL) in exacerbation and remission phases of the disease as well as in skin lesions. Methods: We performed a simultaneous detection of perforin (intracellular molecule) and cell surface antigens on PBL by flow cytometry, and skin lesions were investigated by immunohistochemistry. Results: The most interesting finding was a significant increase of perforin expression in cytotoxic T lymphocytes (CD3+perforin+cells) in the exacerbation phase of disease(P < 0.05), which was mostly located in the CD8+subpopulation (CD8+perforin+) (P < 0.01). Using immunohistochemistry we confirmed the infiltration of T lymphocytes in skin lesions, especially of CD4+and CD8+phenotypes, compared with uninvolved (P < 0.05) and healthy skin (P < 0.01). The expression of perforin was also significantly higher in lesional skin compared with nonlesional and healthy skin (P < 0.05). Conclusions: Our results clearly show the upregulation of perforin expression in peripheral blood as well as in lesions of patients with lichen planus and therefore suggest an important role for perforin in this autoimmune disease.展开更多
文摘Tubulointerstitial lesions, occurring in many kinds of renal diseases, have been found to be the predominant factor in the impairment of renal function. The severe and extensive lesions often predict a poor outcome in future. It has been tested recent years that the infiltrating inflammatory cells might play important roles in the onset and deterioration of tubulointerstitial injuries. On the other hand, the resident cells, including the tubular epithelial cells and the fibroblasts, also directly take part in tubulointerstitial inflammation and fibrosis. Researches also display implicated interactions between the infiltrating cells and the resident cells, which contribute to the amplification of inflammation and the progress of fibrosis.
文摘Background: CD4+ and CD8+ T lymphocytes play different roles in the outcome of leishmaniasis. However, T- cell distribution in lesions shows significant variability in in situ immunocytochemical studies. Objectives: In this report flow cytometry was used to determine the predominant T- cell subsets in leishmaniasis lesions, and their relationship with Leishmania- responsive circulating T cells. Patients and methods: Mononuclear cells from lesions or peripheral blood (PBMC) of 34 cutaneous (CL), four mucosal (ML) and four disseminated leishmaniasis were phenotypically characterized by flow cytometry. Leishmania- responsive T cells were obtained after in vitro stimulation of PBMC with leishmanial antigens. Results/conclusions: Variable amounts of γ δ lymphocytes were present in all lesions, with no association with duration of illness. The highest percentages of interleukin- 2R- and interferon- γ R- positive cells were observed in ML lesions and could render these T cells more susceptible to the effects of these cytokines. The distribution of intralesional T- lymphocyte subsets was quite variable (CD4+ > CD8+ =18 cases, CD8+ >CD4+ =12 cases and CD4+ CD8+ =4 cases) without any association with clinical parameters, and could explain the controversy regarding proportions of these T- cell subsets in leishmaniasis lesions. Low percentages of Leishmania- reactive CD8+ T cells were observed in blood while an enrichment of CD8+ cells was shown in the inflammatory infiltrate, suggesting that local immunoregulatory factors could favour the recruitment and/or proliferation of local CD8+ lymphocytes. Increased percentages of CD8+ cells observed in older lesions are consistent with the hypothesis that they can mediate healing, although their involvement in tissue damage cannot be ruled out. It is possible that these mechanisms can influence the clinical outcome or even the response to therapy.
文摘Background: There have been only two reports on immunophenotypic characteriza tion in the cutaneous lesions of dermatomyositis (DM) that emphasize the importa nce of the infiltrating CD4+ T lymphocytes. Objectives: To characterize the imm unophenotype of the cells that infiltrate the lesional skin of DM and to evaluat e the possible T-helper (Th) polarization Th1/Th2 through detection of specifi c cytokines, chemokine receptors and markers of cellular activation. Methods: Sk in biopsy specimens derived from pathognomonic lesions (Gottron’s papules and Gottron’s sign) of eight patients withDMwere immunostainedwith a large panel o fmonoclonal antibodies to CD3, CD4, CD8, myeloperoxidase(MPO), eosinophil cation ic protein, tryptase, CD40, CD40 ligand (CD40L), HLA-DR, interleukin (IL)- 2, IL- 4, IL- 5, IL- 13, interferon-γ , tumour necrosis factor-α , recept or 3 for CXC chemokines (CXCR3) and receptor 3 for CC chemokines, using the alka line phosphatase-antialkaline phosphatase method. Control specimens were obtai ned from five healthy subjects and from six patients with discoid lupus erythema tosus. Results: Activated CD4+ Th lymphocytes (HLA-DR+ CD40L+ ) were the principal infiltrating cells in the lesional skin of DM; the CD4/CD8 ratio was a pproximately 2· 5. A mixed Th1/Th2 profile and higher Th1 cytokine production t ogether with significant staining for CXCR3 were detected. Neutrophil granulocyt es were the second most abundant population; eosinophil granulocytes were very p oorly represented. Conclusions: Activated CD4+ T cells presumably mediate the main pathogenetic mechanisms in pathognomonic skin lesions. The interaction betw een CD40 andCD40L could be an important mecha nismof cellular activation in cutaneous immune-mediated inflammation by ind uction of secretion of proinflammatory cytokines and chemokines. Neither Th1 nor Th2 clear polarization was found, although there was a slight Th1 prevalence. T here was a significant quantity of MPO+ cells (neutrophil granulocytes) in the in-flamed tissue, and they might have a role in sustaining the chronic inflam mation.
文摘Background: Current evidence suggests that lichen planus is a T-cell-mediated autoimmune disease in which cytotoxic mechanisms have been poorly investigated. Objectives: We investigated the expression of perforin in subpopulations of peripheral blood lymphocytes(PBL) in exacerbation and remission phases of the disease as well as in skin lesions. Methods: We performed a simultaneous detection of perforin (intracellular molecule) and cell surface antigens on PBL by flow cytometry, and skin lesions were investigated by immunohistochemistry. Results: The most interesting finding was a significant increase of perforin expression in cytotoxic T lymphocytes (CD3+perforin+cells) in the exacerbation phase of disease(P < 0.05), which was mostly located in the CD8+subpopulation (CD8+perforin+) (P < 0.01). Using immunohistochemistry we confirmed the infiltration of T lymphocytes in skin lesions, especially of CD4+and CD8+phenotypes, compared with uninvolved (P < 0.05) and healthy skin (P < 0.01). The expression of perforin was also significantly higher in lesional skin compared with nonlesional and healthy skin (P < 0.05). Conclusions: Our results clearly show the upregulation of perforin expression in peripheral blood as well as in lesions of patients with lichen planus and therefore suggest an important role for perforin in this autoimmune disease.
