Session Type: Poster Session (Monday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Autoreactive T-B cell interactions in lymphoid tissue have been thought to play a crucial role in the autoantibody production in systemic lupus erythematosus (SLE). These CD4+T cells are known as follicular helper T (TFH) cells expressing CXCR5, a chemokine receptor promoting cell migration to B cell follicles. Recently, a new population of ‘peripheral helper’ T (TPH) cells that help B cell responses has been discovered in synovium of patients with rheumatoid arthritis. Like TFH cells, TPH cells express ICOS and PD-1, but these cells lack CXCR5. Previously we reported that circulating TPH cells are increased in SLE and their activated status was associated with the disease activity. Here we assessed whether TPH cells contribute to autoantibody production by B cells in SLE.
Methods: Peripheral blood mononuclear cells collected from SLE patients and healthy individuals were analyzed for T and B cell subsets by flow cytometry. TPH cells were identified as CD3+CD4+CD45RA–CXCR5– cells with a high expression of PD-1. The production of IL-21 by TPH cells stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin was assessed by intracellular cytokine staining and flow cytometry. To assess functional roles of TPH cells in B cell maturation and antibody production, T cell populations (TPH, TFH, and CXCR5–PD-1–memory CD4+T cells)and switched memory B (CD19+CD27+IgD–) cells were sorted from PBMC using magnetic bead selection and a FACS Aria sorter. Sorted T cell populations and autologous B cells were co-cultured and stimulated with lipopolysaccharide (LPS) and staphylococcus enterotoxin B (SEB) for 7 days. Plasmablast differentiation was assessed by flow cytometry. Antibody levels in culture supernatants were measured by ELISA.
Results: Activated TPH cells were positively correlated with SLEDAI and anti-DNA antibody titers, and were negatively correlated with serum complement levels and lymphocyte counts. The frequency of activated TPH cells was correlated with that of plasmablasts and activated switched memory B cells. Lupus TPH cells had the capacity to produce IL-21, a pivotal cytokine for B cell and plasma cell differentiation, as much as TFH cells. TPH cells from lupus patients induced B cell differentiation into plasmablasts and promoted antibody production in T-B cell co-cultures.
Conclusion: Our data demonstrate that the increased frequency and activated status of TPH cells are associated with the disease activity as well as enhanced B cell responses in SLE, and TPH cells provide B cell help. CD4+ICOS+PD-1+cells and plasma cells were reported to be present in the nephritic kidneys and associated with active disease in SLE. These data indicate the contribution of TPH cells to autoantibody production in aberrant lymphoid organs and the involvement of extra-follicular T-B cell interactions in the pathogenesis of SLE.
To cite this abstract in AMA style:Makiyama A, Chiba A, Noto D, Murayama G, Mizuno T, Kuga T, Yamaji K, Tamura N, Miyake S. Expanded Circulating Peripheral Helper T Cells Are Associated with B Cell Differentiation in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/expanded-circulating-peripheral-helper-t-cells-are-associated-with-b-cell-differentiation-in-systemic-lupus-erythematosus/. Accessed January 16, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expanded-circulating-peripheral-helper-t-cells-are-associated-with-b-cell-differentiation-in-systemic-lupus-erythematosus/