scholarly journals Minor Histocompatibility Antigen-Specific MHC-Restricted CD8 T Cell Responses Elicited by Heat Shock Proteins

2002 ◽  
Vol 168 (4) ◽  
pp. 1697-1703 ◽  
Author(s):  
Jacques Robert ◽  
Jennifer Gantress ◽  
Laura Rau ◽  
Alisa Bell ◽  
Nicholas Cohen
Keyword(s):  
T Cell ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Histocompatibility Antigen ◽  
Minor Histocompatibility Antigen ◽  
Cell Responses ◽  
Shock Proteins

T Cells Response and Autoantibodies to Human Heat Shock Proteins in Aplastic Anemia Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2403-2403
Author(s):  
Yunfeng Cheng ◽  
Yong Tang ◽  
Neal S. Young
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Aplastic Anemia ◽  
T Cell Proliferation ◽  
Control Group ◽  
Cell Responses ◽  
Shock Proteins

Abstract Heat shock proteins (HSP) have been implicated in autoimmune diseases such as type I diabetes mellitus, systemic lupus erythematosus, and multiple sclerosis, in which T cell proliferative responses or autoantibodies towards endogenous HSP have been detected (Journal of Autoimmunity2003;20:313). HSP70 can function as an endogenous ‘danger’ signal, acting on antigen-presenting cells and critically influencing the decision between induction of tolerance and immunity upon antigen encounter (Millar et al. Nature Medicine2003; 9:1469). We studied T-cell proliferative responses and auto-antibodies to human HSP60, HSP70 and HSP90 proteins in 20 newly diagnosed aplastic anemia patients, peripheral blood was obtained (11 females, 9 males; age average 36.1±19 years). A non-isotopic immunoassay was used for BrdU incorporation into proliferative T cells and ELISA to measure HSP antibody titer. T cell proliferation was measured as the Eu-fluorescence in a time-resolved fluorometer. A positive result was defined as > 2 standard deviations (SD) from the mean of the controls. T-cell responses to HSP70 in the patient group (N=20; mean±SD Eu-fluorescence= 47,129±36,248) were significantly greater than those of the control group (N=18 healthy adult; mean Eu-fluorescence= 23,941±12,996; p=0.01). Fifty percent of the patients showed increased T cell proliferation after HSP70 stimulation compared to 5% in the control group (p=0.03). T-cell responses of the patient group to HSP90 and HSP60 were similar to those of the control group. Twenty percent of patients showed increased T cell proliferation to HSP 60 and HSP 90 stimulation compared to 5% in the control group (p=0.363). HSP antibody (IgG/A/M) seropositivity was 25% to HSP60, 50% to HSP70, and 5% to HSP90 in patients and 8% to HSP60, 0% to HSP70, and 0% to HSP90 in controls. Heightened autoimmunity to HSP70, but not to HSP60 and HSP90, is a feature of acquired aplastic anemia at presentation.

scholarly journals Minor Histocompatibility Antigen DDX3Y Induces HLA-DQ5-Restricted T Cell Responses with Limited TCR-Vβ Usage Both In Vivo and In Vitro

2006 ◽  
Vol 12 (11) ◽  
pp. 1114-1124 ◽  
Author(s):  
David Laurin ◽  
Eric Spierings ◽  
Lars T. van der Veken ◽  
Abdelbasset Hamrouni ◽  
J.H. Frederik Falkenburg ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Histocompatibility Antigen ◽  
Minor Histocompatibility Antigen ◽  
Cell Responses

scholarly journals Targeting of tolerogenic dendritic cells to heat-shock proteins in inflammatory arthritis

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Rachel Spiering ◽  
Manon A. A. Jansen ◽  
Matthew J. Wood ◽  
Anshorulloh A. Fath ◽  
Oliver Eltherington ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Inflammatory Arthritis ◽  
Cell Responses ◽  
Tolerogenic Dendritic Cells ◽  
Healthy Donors ◽  
Shock Proteins

Abstract Background Autologous tolerogenic dendritic cells (tolDC) are a promising therapeutic strategy for inflammatory arthritis (IA) as they can regulate autoantigen-specific T cell responses. Here, we investigated two outstanding priorities for clinical development: (i) the suitability of using heat-shock proteins (HSP), abundant in inflamed synovia, as surrogate autoantigens to be presented by tolDC and (ii) identification of functional biomarkers that confirm tolDC regulatory activity. Methods Cell proliferation dye-labelled human peripheral blood mononuclear cells of IA (rheumatoid arthritis (RA) and psoriatic arthritis (PsA)) patients or healthy donors were cultured with HSP40-, HSP60- and HSP70-derived peptides or recall antigens (e.g. tuberculin purified protein derivative (PPD)) in the presence or absence of tolDC or control DC for 9 days. Functional characteristics of proliferated antigen-specific T-cells were measured using flow cytometry, gene expression profiling and cytokine secretion immunoassays. Repeated measures analysis of variance (ANOVA) with Bonferroni correction for comparisons between multiple groups and paired Student t test for comparisons between two groups were used to determine significance. Results All groups showed robust CD4+ T-cell responses towards one or more HSP-derived peptide(s) as assessed by a stimulation index > 2 (healthy donors: 78%, RA: 73%, PsA: 90%) and production of the cytokines IFNγ, IL-17A and GM-CSF. Addition of tolDC but not control DC induced a type 1 regulatory (Tr1) phenotype in the antigen-specific CD4+ T-cell population, as identified by high expression of LAG3, CD49b and secretion of IL-10. Furthermore, tolDC inhibited bystander natural killer (NK) cell activation in a TGFβ dependent manner. Conclusions HSP-specific CD4+ T-cells are detectable in the majority of RA and PsA patients and can be converted into Tr1 cells by tolDC. HSP-loaded tolDC may therefore be suitable for directing T regulatory responses to antigens in inflamed synovia of IA patients. Tr1 markers LAG3, CD49b and IL-10 are suitable biomarkers for future tolDC clinical trials.

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