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Reduced response to Epstein-Barr virus antigens by T-cells in systemic lupus erythematosus patients.

Draborg AH, Jacobsen S, Westergaard M, Mortensen S, Larsen JL, Houen G, Duus K - Lupus Sci Med (2014)

Bottom Line: Epstein-Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE).These results indicate a limited or a defective EBV-specific T-cell response in SLE patients, which may suggest poor control of EBV infection in SLE with an immune reaction shift towards a humoral response in an attempt to control viral reactivation.A role for decreased control of EBV as a contributing agent in the development or exacerbation of SLE is proposed.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Biochemistry, Immunology and Genetics , Statens Serum Institut , Copenhagen , Denmark.

ABSTRACT

Objective: Epstein-Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE). In this study, we investigated the levels of latent and lytic antigen EBV-specific T-cells and antibodies in SLE patients.

Methods: T cells were analyzed by flow cytometry and antibodies were analyzed by enzyme-linked immunosorbent assay.

Results: SLE patients showed a significantly reduced number of activated (CD69) T-cells upon ex vivo stimulation with EBV nuclear antigen (EBNA) 1 or EBV early antigen diffuse (EBV-EA/D) in whole blood samples compared with healthy controls. Also, a reduced number of T-cells from SLE patients were found to produce interferon-γ upon stimulation with these antigens. Importantly, responses to a superantigen were normal in SLE patients. Compared with healthy controls, SLE patients had fewer EBV-specific T-cells but higher titres of antibodies against EBV. Furthermore, an inverse correlation was revealed between the number of lytic antigen EBV-specific T-cells and disease activity of the SLE patients, with high-activity SLE patients having fewer T-cells than low-activity SLE patients.

Conclusions: These results indicate a limited or a defective EBV-specific T-cell response in SLE patients, which may suggest poor control of EBV infection in SLE with an immune reaction shift towards a humoral response in an attempt to control viral reactivation. A role for decreased control of EBV as a contributing agent in the development or exacerbation of SLE is proposed.

No MeSH data available.


Related in: MedlinePlus

Activated T-cells in SLE patients and healthy controls upon EBV antigen stimulation. Heparinised whole blood samples from SLE patients (n=22) and sex-matched and age-matched healthy controls (n=22) were stimulated with EBNA1 (A) and EBV-EA/D (B). The percentages of activated T-cells (with bound CD69 antibodies) are shown divided into the total number of CD69 T-cells and CD8 and CD4 (CD8−) T-cells expressing CD69, respectively. Data are represented as mean±SEM. p Values for comparison of SLE patients and healthy controls are 0.0001, 0.0007 and <0.0001 regarding total, CD8 and CD4 CD69-expressing T-cells upon EBNA1 stimulation, respectively (A), and 0.0015, 0.0103 and 0.0005 regarding total, CD8 and CD4 CD69-expressing T-cells upon EBV-EA/D stimulation, respectively (B). SLE, systemic lupus erythematosus; EBNA1, Epstein–Barr virus nuclear antigen 1; EBV-EA/D, Epstein–Barr virus early antigen diffuse.
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LUPUS2014000015F2: Activated T-cells in SLE patients and healthy controls upon EBV antigen stimulation. Heparinised whole blood samples from SLE patients (n=22) and sex-matched and age-matched healthy controls (n=22) were stimulated with EBNA1 (A) and EBV-EA/D (B). The percentages of activated T-cells (with bound CD69 antibodies) are shown divided into the total number of CD69 T-cells and CD8 and CD4 (CD8−) T-cells expressing CD69, respectively. Data are represented as mean±SEM. p Values for comparison of SLE patients and healthy controls are 0.0001, 0.0007 and <0.0001 regarding total, CD8 and CD4 CD69-expressing T-cells upon EBNA1 stimulation, respectively (A), and 0.0015, 0.0103 and 0.0005 regarding total, CD8 and CD4 CD69-expressing T-cells upon EBV-EA/D stimulation, respectively (B). SLE, systemic lupus erythematosus; EBNA1, Epstein–Barr virus nuclear antigen 1; EBV-EA/D, Epstein–Barr virus early antigen diffuse.

Mentions: Figure 2 illustrates the percentages of T-cells (CD3) from SLE patients and HCs that express CD69 on their surface (activated) upon stimulation with EBNA1 (figure 2A) and EBV-EA/D (figure 2B). Results showed a statistically significant reduced level of both EBNA1-specific and EA/D-specific T-cells in SLE patients compared with HCs. The reaction to EBNA1 was shown especially to be reduced in the SLE patients. The SLE patients experienced a weaker response to the EBV antigens compared with the HCs with statistically significant fewer T-cells, both CD8 and CD4, becoming activated (p=0.0001, 0.0007 and <0.0001 regarding total, CD8 and CD4, CD69-expressing T-cells upon EBNA1 stimulation, respectively, in figure 2A, and p=0.0015, 0.0103 and 0.0005 regarding total, CD8 and CD4, CD69-expressing T-cells upon EBV-EA/D stimulation, respectively, in figure 2B).


Reduced response to Epstein-Barr virus antigens by T-cells in systemic lupus erythematosus patients.

Draborg AH, Jacobsen S, Westergaard M, Mortensen S, Larsen JL, Houen G, Duus K - Lupus Sci Med (2014)

Activated T-cells in SLE patients and healthy controls upon EBV antigen stimulation. Heparinised whole blood samples from SLE patients (n=22) and sex-matched and age-matched healthy controls (n=22) were stimulated with EBNA1 (A) and EBV-EA/D (B). The percentages of activated T-cells (with bound CD69 antibodies) are shown divided into the total number of CD69 T-cells and CD8 and CD4 (CD8−) T-cells expressing CD69, respectively. Data are represented as mean±SEM. p Values for comparison of SLE patients and healthy controls are 0.0001, 0.0007 and <0.0001 regarding total, CD8 and CD4 CD69-expressing T-cells upon EBNA1 stimulation, respectively (A), and 0.0015, 0.0103 and 0.0005 regarding total, CD8 and CD4 CD69-expressing T-cells upon EBV-EA/D stimulation, respectively (B). SLE, systemic lupus erythematosus; EBNA1, Epstein–Barr virus nuclear antigen 1; EBV-EA/D, Epstein–Barr virus early antigen diffuse.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225738&req=5

LUPUS2014000015F2: Activated T-cells in SLE patients and healthy controls upon EBV antigen stimulation. Heparinised whole blood samples from SLE patients (n=22) and sex-matched and age-matched healthy controls (n=22) were stimulated with EBNA1 (A) and EBV-EA/D (B). The percentages of activated T-cells (with bound CD69 antibodies) are shown divided into the total number of CD69 T-cells and CD8 and CD4 (CD8−) T-cells expressing CD69, respectively. Data are represented as mean±SEM. p Values for comparison of SLE patients and healthy controls are 0.0001, 0.0007 and <0.0001 regarding total, CD8 and CD4 CD69-expressing T-cells upon EBNA1 stimulation, respectively (A), and 0.0015, 0.0103 and 0.0005 regarding total, CD8 and CD4 CD69-expressing T-cells upon EBV-EA/D stimulation, respectively (B). SLE, systemic lupus erythematosus; EBNA1, Epstein–Barr virus nuclear antigen 1; EBV-EA/D, Epstein–Barr virus early antigen diffuse.
Mentions: Figure 2 illustrates the percentages of T-cells (CD3) from SLE patients and HCs that express CD69 on their surface (activated) upon stimulation with EBNA1 (figure 2A) and EBV-EA/D (figure 2B). Results showed a statistically significant reduced level of both EBNA1-specific and EA/D-specific T-cells in SLE patients compared with HCs. The reaction to EBNA1 was shown especially to be reduced in the SLE patients. The SLE patients experienced a weaker response to the EBV antigens compared with the HCs with statistically significant fewer T-cells, both CD8 and CD4, becoming activated (p=0.0001, 0.0007 and <0.0001 regarding total, CD8 and CD4, CD69-expressing T-cells upon EBNA1 stimulation, respectively, in figure 2A, and p=0.0015, 0.0103 and 0.0005 regarding total, CD8 and CD4, CD69-expressing T-cells upon EBV-EA/D stimulation, respectively, in figure 2B).

Bottom Line: Epstein-Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE).These results indicate a limited or a defective EBV-specific T-cell response in SLE patients, which may suggest poor control of EBV infection in SLE with an immune reaction shift towards a humoral response in an attempt to control viral reactivation.A role for decreased control of EBV as a contributing agent in the development or exacerbation of SLE is proposed.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Biochemistry, Immunology and Genetics , Statens Serum Institut , Copenhagen , Denmark.

ABSTRACT

Objective: Epstein-Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE). In this study, we investigated the levels of latent and lytic antigen EBV-specific T-cells and antibodies in SLE patients.

Methods: T cells were analyzed by flow cytometry and antibodies were analyzed by enzyme-linked immunosorbent assay.

Results: SLE patients showed a significantly reduced number of activated (CD69) T-cells upon ex vivo stimulation with EBV nuclear antigen (EBNA) 1 or EBV early antigen diffuse (EBV-EA/D) in whole blood samples compared with healthy controls. Also, a reduced number of T-cells from SLE patients were found to produce interferon-γ upon stimulation with these antigens. Importantly, responses to a superantigen were normal in SLE patients. Compared with healthy controls, SLE patients had fewer EBV-specific T-cells but higher titres of antibodies against EBV. Furthermore, an inverse correlation was revealed between the number of lytic antigen EBV-specific T-cells and disease activity of the SLE patients, with high-activity SLE patients having fewer T-cells than low-activity SLE patients.

Conclusions: These results indicate a limited or a defective EBV-specific T-cell response in SLE patients, which may suggest poor control of EBV infection in SLE with an immune reaction shift towards a humoral response in an attempt to control viral reactivation. A role for decreased control of EBV as a contributing agent in the development or exacerbation of SLE is proposed.

No MeSH data available.


Related in: MedlinePlus