Background.Several studies have investigated levels of T-cell-derived interleukin(IL)-10 in individuals with atopic dermatitis,with conflicting results.Aims/Hypothesis.In order to address whether stratification of dis...Background.Several studies have investigated levels of T-cell-derived interleukin(IL)-10 in individuals with atopic dermatitis,with conflicting results.Aims/Hypothesis.In order to address whether stratification of disease severity may help resolve the different findings,the hypothesis was tested that individuals with severe atopic dermatitis have a lower frequency of circulating IL-10-producing,allergen-specific CD4+T cells than do individuals with mild disease.Methods.Using peripheral blood mononuclear cells derived from individuals with severe(n = 12)and mild atopic dermatitis(n = 10)and from nonatopic controls(n = 10),we investigated production by CD4+T cells of tumour necrosis factor(TNF)-α,IL-4,IL-5,IL-13 and IL-10 in response to phorbol myristate acetate/ionomycinand Der p1 allergen.Results.It was observed that there were significantly higher frequencies of allergen-specific circulating CD4+T cells producing TNF-α-IL-4-,IL-5-and IL-13,and lower frequencies of these cells producing IL-10 in individuals with severe atopic dermatitis compared with mildly affected individuals and nonatopic controls(P < 0.01 for all comparisons).Furthermore,the Der p1-specific CD4+T cells were enriched within the subset of cells positive for cutaneous lymphocyte-associated antigen.Conclusions.Analysis of levels of allergen-specific CD4+T-cell production of IL-10 in relation to disease severity argues in favour of a role for IL-10 in the control of atopic dermatitis.展开更多
Background: Systemic immunosuppression is a significant risk factor for cutaneous squamous cell carcinoma (SCC). p53 is mutated and overexpressed in up to 90% of cutaneous SCC lesions. Despite considerable evidence th...Background: Systemic immunosuppression is a significant risk factor for cutaneous squamous cell carcinoma (SCC). p53 is mutated and overexpressed in up to 90% of cutaneous SCC lesions. Despite considerable evidence that the immune response is important in the control of cutaneous SCC, there are no studies documenting potential tumour- associated antigens. Objectives: We tested the hypothesis that individualswith cutaneous SCC have functional circulating CD8+ T cells specific for p53. Methods: Interferon- γ immunosorbent assays were used to screen peripheral blood mononuclear cells for reactivity to six p53- derived HLA- A 0201- restricted epitopes from HLA- A 0201- positive patients and controls. Results: We observed significantly elevated frequencies of p53- specific CD8+ T cells in seven of 26 individuals with cutaneous SCC and in one of 10 controls. The degree of lymphocytic infiltrate significantly correlated with the frequency of CD8+ T cells specific for p53 epitopes, but not with control epitopes. Conclusions: Overall, these data suggest that p53 may represent a target for CD8+ T cells in a proportion of individuals with cutaneous SCC.展开更多
Background:Mucous membrane pemphigoid (MMP) is a chronic blistering skin dise ase frequently associated with circul atingautoantibodies directed to a number o f antigens including the NC16A region of BP180. NC16A doma...Background:Mucous membrane pemphigoid (MMP) is a chronic blistering skin dise ase frequently associated with circul atingautoantibodies directed to a number o f antigens including the NC16A region of BP180. NC16A domain-specific T cells h ave been identified in the blood of individuals with bullous pemphigoid (BP), pe mphigoid gestationis and linear IgA disease, but there are no data investigating the potential role for such T cells in the pathogenesis of MMP. Objectives:To test the hypothesis that NC16A-specific T cells exist in the peripheral blood o f individuals with MMP. Methods:We isolated peripheral blood mononuclear cells from 10 patients with MMP, 17 with BP and 10 healthy controls and examined the i mmunogenicity of overlapping peptides spanning the NC16A domain using interferon (IFN)-γenzyme-linked immunospot assay. Results:Significant IFN-γproductio n was observed in response to the NC16A peptides in two of the patients with MMP and two of the patients with BP but in none of the normal controls. These data suggest that in a minority of individuals with MMP, NC16A domain-specific T cel ls circulate at sufficiently high frequency to be detectable directly ex vivo an d to show rapid effector function. Conclusions:Overall, these findings are the first to examine the potential role for antigen-specific autoreactive T cells i n the pathogenesis of MMP, and confirm that in some individuals the NC16A domain may be an important target antigen.展开更多
文摘Background.Several studies have investigated levels of T-cell-derived interleukin(IL)-10 in individuals with atopic dermatitis,with conflicting results.Aims/Hypothesis.In order to address whether stratification of disease severity may help resolve the different findings,the hypothesis was tested that individuals with severe atopic dermatitis have a lower frequency of circulating IL-10-producing,allergen-specific CD4+T cells than do individuals with mild disease.Methods.Using peripheral blood mononuclear cells derived from individuals with severe(n = 12)and mild atopic dermatitis(n = 10)and from nonatopic controls(n = 10),we investigated production by CD4+T cells of tumour necrosis factor(TNF)-α,IL-4,IL-5,IL-13 and IL-10 in response to phorbol myristate acetate/ionomycinand Der p1 allergen.Results.It was observed that there were significantly higher frequencies of allergen-specific circulating CD4+T cells producing TNF-α-IL-4-,IL-5-and IL-13,and lower frequencies of these cells producing IL-10 in individuals with severe atopic dermatitis compared with mildly affected individuals and nonatopic controls(P < 0.01 for all comparisons).Furthermore,the Der p1-specific CD4+T cells were enriched within the subset of cells positive for cutaneous lymphocyte-associated antigen.Conclusions.Analysis of levels of allergen-specific CD4+T-cell production of IL-10 in relation to disease severity argues in favour of a role for IL-10 in the control of atopic dermatitis.
文摘Background: Systemic immunosuppression is a significant risk factor for cutaneous squamous cell carcinoma (SCC). p53 is mutated and overexpressed in up to 90% of cutaneous SCC lesions. Despite considerable evidence that the immune response is important in the control of cutaneous SCC, there are no studies documenting potential tumour- associated antigens. Objectives: We tested the hypothesis that individualswith cutaneous SCC have functional circulating CD8+ T cells specific for p53. Methods: Interferon- γ immunosorbent assays were used to screen peripheral blood mononuclear cells for reactivity to six p53- derived HLA- A 0201- restricted epitopes from HLA- A 0201- positive patients and controls. Results: We observed significantly elevated frequencies of p53- specific CD8+ T cells in seven of 26 individuals with cutaneous SCC and in one of 10 controls. The degree of lymphocytic infiltrate significantly correlated with the frequency of CD8+ T cells specific for p53 epitopes, but not with control epitopes. Conclusions: Overall, these data suggest that p53 may represent a target for CD8+ T cells in a proportion of individuals with cutaneous SCC.
文摘Background:Mucous membrane pemphigoid (MMP) is a chronic blistering skin dise ase frequently associated with circul atingautoantibodies directed to a number o f antigens including the NC16A region of BP180. NC16A domain-specific T cells h ave been identified in the blood of individuals with bullous pemphigoid (BP), pe mphigoid gestationis and linear IgA disease, but there are no data investigating the potential role for such T cells in the pathogenesis of MMP. Objectives:To test the hypothesis that NC16A-specific T cells exist in the peripheral blood o f individuals with MMP. Methods:We isolated peripheral blood mononuclear cells from 10 patients with MMP, 17 with BP and 10 healthy controls and examined the i mmunogenicity of overlapping peptides spanning the NC16A domain using interferon (IFN)-γenzyme-linked immunospot assay. Results:Significant IFN-γproductio n was observed in response to the NC16A peptides in two of the patients with MMP and two of the patients with BP but in none of the normal controls. These data suggest that in a minority of individuals with MMP, NC16A domain-specific T cel ls circulate at sufficiently high frequency to be detectable directly ex vivo an d to show rapid effector function. Conclusions:Overall, these findings are the first to examine the potential role for antigen-specific autoreactive T cells i n the pathogenesis of MMP, and confirm that in some individuals the NC16A domain may be an important target antigen.
