The role of CD8+ T-cell systemic lupus erythematosus pathogenesis: an update

Abstract

Purpose of review: Systemic lupus erythematosus (SLE) is a serious autoimmune disease with a wide range of organ involvement. In addition to aberrant B-cell responses leading to autoantibody production, T-cell abnormalities are important in the induction of autoimmunity and the ensuing downstream organ damage. In this article, we present an update on how subsets of CD8+ T cells contribute to SLE pathogenesis.

Recent findings: Reduced cytolytic function of CD8+ T cells not only promotes systemic autoimmunity but also accounts for the increased risk of infections. Additional information suggests that effector functions of tissue CD8+ T cells contribute to organ damage. The phenotypic changes in tissue CD8+ T cells likely arise from exposure to tissue microenvironment and crosstalk with tissue resident cells. Research on pathogenic IL-17-producing double negative T cells also suggests their origin from autoreactive CD8+ T cells, which also contribute to the induction and maintenance of systemic autoimmunity.

Summary: Reduced CD8+ T-cell effector function illustrates their role in peripheral tolerance in the control of autoimmunity and to the increased risk of infections. Inflammatory cytokine producing double negative T cells and functional defects of regulatory CD8+ T cell both contribute to SLE pathogenesis. Further in depth research on these phenotypic changes are warranted for the development of new therapeutics for people with SLE.

FIGURE 1.

Immunopathology of various CD8⁺ T-cell subtypes and contribution to pathogenesis. Reduced cytolytic function of systemic CD8⁺ is related to the expanded CD38⁺ subpopulation and correlates with the increased risk of infection. Functional defects of cytotoxic T cells also result in failure to remove autoreactive B cells and thus increase autoantibody producing cells. Functional defects in regulatory CD8⁺ T cells also contribute to the loss of peripheral tolerance. Meanwhile, methylation of Cd8 locus through cAMP-responsive element modulator α and the inflammatory milieu lead to generation and expansion of IL-17-producing CD4⁻CD8⁻double negative T cells. Tissue infiltrating CD8⁺ T-cell cause tissue damage as a result of exposure to changes in tissue metabolic factors, such as hypoxia and arginine levels.