Preserved specific anti-viral T-cell response but associated with decreased lupus activity in SLE patients with cytomegalovirus infection

Rheumatology (Oxford). 2020 Nov 1;59(11):3340-3349. doi: 10.1093/rheumatology/keaa143.

Abstract

Objectives: SLE is an autoimmune disease characterized by aberrant autoantibody production and immune dysfunctions. Whether the anti-CMV immunity is impaired in SLE patients is poorly understood. We investigated the specific anti-viral T-cell response in SLE patients with CMV infection and its possible impacts on clinical manifestations in lupus.

Methods: CD28 null T-cell percentages were measured by flow cytometry in 89 SLE patients and 58 healthy controls. A specific anti-CMV CD8 T-cell response was assessed ex vivo by the production of intracellular cytokines in response to CMV phosphoprotein 65 (pp65) by flow cytometry. Clinical manifestations and immune parameters were analysed in SLE patients according to their CMV serostatus.

Results: CD28 null T cells were significantly expanded in SLE patients. When the anti-CMV pp65 CD8 polyfunctional T cell response was analysed, as defined by production of at least three of four functional cytokines or effectors (intracellular IFN-γ, IL-2, TNF-α and surface CD107a), the results demonstrated that it was not impaired in SLE patients. In contrast, when comparing clinical manifestations, there were lower anti-ds-DNA levels and decreased SLEDAI in SLE patients with CMV infection. Furthermore, the expansion of CD4+CD28 null T cells was negatively associated with anti-ds-DNA levels and SLEDAI in these lupus patients.

Conclusion: In SLE patients with CMV infection, the specific anti-CMV CD8 T-cell response is preserved but is associated with decreased disease activity and lower anti-DNA levels among these patients, suggesting CMV infection may mitigate lupus activity.

Keywords: CD28 null T cells; SLE disease activity; cytomegalovirus; polyfunctional CD8 T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / blood
  • Antibody Specificity
  • CD28 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / blood
  • Cytomegalovirus Infections / immunology*
  • DNA / immunology
  • Female
  • Flow Cytometry
  • Humans
  • Immunity, Cellular
  • Immunoglobulin G / blood
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / biosynthesis
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocyte Activation
  • Lymphocytes, Null / immunology
  • Lysosomal-Associated Membrane Protein 1 / biosynthesis
  • Male
  • Middle Aged
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Viral Matrix Proteins / immunology*

Substances

  • Antibodies, Viral
  • CD28 Antigens
  • Immunoglobulin G
  • Interleukin-2
  • Lysosomal-Associated Membrane Protein 1
  • Tumor Necrosis Factor-alpha
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • Interferon-gamma
  • DNA