Signaling Lymphocytic Activation Molecule Family Member 1 Engagement Inhibits T Cell–B Cell Interaction and Diminishes Interleukin-6 Production and Plasmablast Differentiation in Systemic Lupus Erythematosus

Maria P. Karampetsou, Denis Comte, Abel Suárez-Fueyo, Eri Katsuyama, Nobuya Yoshida, Michihito Kono, Vasileios C. Kyttaris, George C. Tsokos

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Objective: Signaling lymphocytic activation molecule family member 1 (SLAMF1) homophilic interactions promote immunoglobulin production and T cell–B cell cross-talk. SLAMF1 is overexpressed on T and B cells in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine the role of SLAMF1 monoclonal antibody (mAb) in modulating T cell–B cell interaction and B cell activation. Methods: Anti-IgM–prestimulated naive or total B cells from either healthy donors or patients with SLE were cocultured with autologous T cells under CD3/CD28 stimulation, in the presence or absence of the SLAMF1 mAb. Naive B cells were stimulated with anti-IgM and CD40L in the presence of the SLAMF1 antibody. Cytokine production by CD4+ T cells and B cells was examined by flow cytometry and/or quantitative polymerase chain reaction. Plasmablast formation and T cell and B cell conjugates were assessed by flow cytometry. IgG and antinuclear antibody production was determined by enzyme-linked immunosorbent assay. Results: SLAMF1 ligation in a human peripheral blood T cell–B cell culture system reduced the following in both healthy controls and patients with SLE: conjugate formation, interleukin-6 (IL-6) production by B cells, IL-21 and IL-17A production by T cells, and Ig and autoantibody production. Whereas the SLAMF1 mAb directly affected the function of isolated peripheral B cells by decreasing IL-6 and Ig production in vitro, it did not affect cytokine production by isolated T cells stimulated in vitro. Conclusion: The SLAMF1 antibody inhibits T cell–B cell interaction and suppresses B cell cytokine production and differentiation, thereby acting as a potential therapeutic tool in the treatment of patients with SLE.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalArthritis and Rheumatology
Volume71
Issue number1
DOIs
Publication statusPublished - Jan 2019
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

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