IL-7Rαlow memory CD8+ T cells are significantly elevated in patients with systemic lupus erythematosus

Rheumatology (Oxford). 2012 Sep;51(9):1587-94. doi: 10.1093/rheumatology/kes100. Epub 2012 Jun 1.

Abstract

Objective: Human effector memory (EM) CD8(+) T cells include IL-7Rα(high) and IL-7Rα(low) cells with distinct cellular characteristics, including the expression of cytotoxic molecules. Both NK cells and the NK cell-associated molecule 2B4 that is expressed on CD8(+) T cells promote cytotoxicity. Here we analysed the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells and its contribution to cytotoxicity. We also analysed the frequency of IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells in patients with SLE or lupus and in healthy individuals given the potential role of cytotoxic CD8(+) T cells in the pathogenesis of lupus.

Methods: We used flow cytometry to measure the expression of 2B4 on IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells as well as the frequency of these cell populations in the peripheral blood of healthy individuals and patients with SLE. Also, 2B4-mediated cytotoxicity was quantitated in IL-7Rα(high) and IL-7Rα(low) EM CD8(+) T cells using target cells with CD48 antigen.

Results: We found that IL-7Rα(high) EM CD8(+) T cells had higher levels of 2B4 expression compared with IL-7Rα(low) EM CD8(+) T cells. Triggering 2B4 enhanced the cytotoxic function of IL-7Rα(low) EM CD8(+) T cells against target cells. We also noticed that patients with SLE had an increased frequency of IL-7Rα(low) EM CD8(+) T cells that correlated with disease manifestation.

Conclusion: Our findings show that SLE patients have increased IL-7Rα(low) EM CD8(+) T cells, possibly contributing to tissue damage through 2B4-mediated cytotoxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Blocking / pharmacology
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Coculture Techniques
  • Cytotoxicity, Immunologic
  • Female
  • Flow Cytometry
  • Humans
  • Immunologic Memory / immunology*
  • Immunophenotyping
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology*
  • Lymphocyte Count
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Receptors, Interleukin-7 / immunology*
  • Receptors, Interleukin-7 / metabolism
  • Signaling Lymphocytic Activation Molecule Family

Substances

  • Antibodies, Blocking
  • Antigens, CD
  • CD244 protein, human
  • Receptors, Immunologic
  • Receptors, Interleukin-7
  • Signaling Lymphocytic Activation Molecule Family
  • interleukin-7 receptor, alpha chain