Distinctive response of thyroid-infiltrating mononuclear cells to B cell activation through CD40 and interleukin-4 in graves' patients

Mitsuyasu Itoh, Keiko Uchimura, Keiko Yamamoto, Masaki Makino, Shigeo Imamura, Takako Kobayashi, Kentaro Fujiwara, Taiya Kato, Nobuki Hayakawa, Yoshikuni Sawai, Akio Nagasaka, Katsumi Iwase, Takahide Nomura, Yasumichi Hagino

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The possible role of abnormal T cell-dependent B-cell activation in Graves' disease was investigated by comparing lymphocyte subset distribution and the production of soluble CD8 (sCD8), sCD23, IL-10 and IL-12 by peripheral blood cells (PBMC) and thyroid-infiltrating lymphocytes (TL) in vitro. In TL, the percentage of CD8+ cells was slightly higher and the sCD8 concentration was significantly higher than in PBMC. The ratio CD23+ cells to CD20+ cells (activated B/pan B cells) was increased in TL compared to PBMC from Graves' or normal controls, although the percentage of CD20+ cells was decreased. Compared to PBMC in Graves' disease, the relative ratio of IL-10 to IL-12 release (IL-10/IL-12) by unstimulated TL was increased, despite a lack of significant difference between PBMC and TL in mean values for either IL-10 or IL-12 secretion. Incubating PBMC with a combination of anti-CD40 monoclonal antibodies and interleukin-4 (IL-4) resulted in B cell activation, reflected in an increase in the sCD23 level in both controls and Graves' patients, but especially prominent in the latter. Stimulation with anti-CD40 antibody and IL-4 also decreased the percentage of CD8+ cells in PBMC but not TL from both Graves' disease and normal controls, and the percentage of CD8+ cells in TL was higher than PBMC after the stimulation. The sCD23 concentration in TL was decreased compared to PBMC both in patients with Graves' disease and normal controls. However, in contrast to the increased responses observed in Graves' PBMC or normal controls after stimulation, sCD23 levels remained the same in stimulated TL from Graves' patients. This combination of B cell stimulants increased production of IL-10 in PBMC but not in TL obtained from patients with Graves' disease, and the increased IL-10/IL-12 ratio declined to a value no different from that in PBMC group after stimulation. Thus, T cell-dependent B-cell activation via a CD40 pathway may cause a shift in the Th1/Th2 balance to Th2 dominance in Graves' disease, while increased CD8+ cells in TL may suppress sCD23 production and IL-10-producing Th2 cells.

Original languageEnglish
Pages (from-to)107-114
Number of pages8
JournalCytokine
Volume19
Issue number3
DOIs
Publication statusPublished - 2002

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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