TY - JOUR
T1 - 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
AU - Karampetsou, Maria P.
AU - Comte, Denis
AU - Suárez-Fueyo, Abel
AU - Katsuyama, Eri
AU - Yoshida, Nobuya
AU - Kono, Michihito
AU - Kyttaris, Vasileios C.
AU - Tsokos, George C.
N1 - Funding Information:
Dr. Comte’s work was supported by the SICPA Foundation. Dr. Suárez-Fueyo’s work was supported by NIH training grant T32-AI-074549. Dr. Tsokos’ work was supported by NIH grants P0-1AI-065687, R01-AI-42269, and R37-AI-49954.
Publisher Copyright:
© 2018, American College of Rheumatology
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
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U2 - 10.1002/art.40682
DO - 10.1002/art.40682
M3 - Article
C2 - 30058241
AN - SCOPUS:85059236175
VL - 71
SP - 99
EP - 108
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 1
ER -