Cytomegalovirus aggravates the autoimmune phenomenon in systemic autoimmune diseases

Microb Pathog. 2018 Jul:120:132-139. doi: 10.1016/j.micpath.2018.04.041. Epub 2018 Apr 26.

Abstract

Background: Human Cytomegalovirus (CMV), because of its ability to extensively manipulate host immunity during active infection, has been suggested to be involved in autoimmunity. However, its influence on T-cells and cytokines in systemic autoimmune diseases like systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is indistinct.

Methods: We investigated the in-vitro response of T lymphocytes from SLE and SSc patients to CMV antigen. Functional activity of T lymphocytes was determined by estimating Th1 (IL-2 and IFN-γ) and Th2 (IL-4 and IL-10) cytokines.

Results: We observed that CMV antigen stimulation in-vitro resulted in significant increase in CD4:CD8 T-cell ratio in peripheral blood mononuclear cells (PBMCs) from SLE and SSc patients; response dominated by CD4+ than CD8+ memory T-cells. SSc T-cell response was differentiated by aberrant increase in CD4+CD25+ T-cells. CMV antigen caused elevation in IL-4 and IFN-γ production in both patient PBMCs, whereas IL-2 was also raised in SLE PBMCs. The development of large pool of memory T-cells and overproduction of IFN-γ may result in flare-up of autoimmunity in these patients.

Conclusion: Our study provides an insight into the immunopathological potential of CMV-reactive immune cells to develop new potential strategies for targeted therapeutic intervention.

Keywords: Autoimmunity; Cytokines; Cytomegalovirus; Systemic lupus erythematosus; Systemic sclerosis; T cells.

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Viral / immunology
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / metabolism*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Child
  • Cytokines / metabolism
  • Cytomegalovirus / immunology*
  • Cytomegalovirus / pathogenicity*
  • Cytomegalovirus Infections / immunology*
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-2 / metabolism
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-4 / metabolism
  • Leukocytes, Mononuclear / immunology
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / virology
  • Male
  • Middle Aged
  • Scleroderma, Systemic / immunology
  • Scleroderma, Systemic / virology
  • T-Lymphocytes / metabolism
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Young Adult

Substances

  • Antigens, Viral
  • Cytokines
  • IL10 protein, human
  • IL4 protein, human
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma