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Background <p>The seroconversion rate after hepatitis B virus (HBV) vaccination in people living with human immunodeficiency virus (HIV) is reportedly lower than that in non-HIV controls. Follicular helper T (Tfh) cells play a central role in humoral immunity, and IL-21 secreted by Tfh cells is essential for B cells to differentiate into plasma cells. This study investigated the frequency and function of circulating Tfh (cTfh) cells isolated from people living with HIV (PWH) who are negative for hepatitis B virus (HBV) surface antigen (HBsAb−) in a small cohort of PWH who received HBV vaccination.</p> Case presentation <p>The frequency of cTfh cells in HBsAb− PWH (HBsAb levels less than 10 mIU/mL) was the same as that in non-HIV controls and HBsAb positive (HBsAb+) PWH, who maintained HBsAb at 10 mIU/mL for at least 1 year after receiving three doses of the HBV vaccine. However, after immune stimulation with anti-CD3/CD28 antibodies, the frequency of cTfh cells in the non-HIV controls and HBsAb+ PWH increased, whereas the frequency of cTfh cells in the HBsAb− PWH tended to be more gradual. cTfh17-like and cTfh2-like cells, subsets of cTfh cells, are involved in humoral immunity, and PD-1 regulates the function of these cells in the germinal center. The frequencies of PD-1+ cTfh17-like and cTfh2-like cells at baseline did not differ significantly among the three groups. However, HBsAb− PWH had a lower frequency of PD-1+ cTfh17-like cells after immune stimulation than non-HIV controls did. The frequencies of PD-1+ cTfh17-like cells and cTfh2-like cells with high PD-1 expression were significantly lower in HBsAb− PWH than in non-HIV controls. Furthermore, the production of IL-21, which is essential for plasma cell differentiation, tended to be lower in HBsAb− PWH than in non-HIV controls or HBsAb+ PWH.</p> Conclusions <p>cTfh cells isolated from HBsAb− PWH may be unable to produce sufficient IL-21 after immune stimulation. This study is the first to suggest that cTfh cells may not function adequately in some PWH. This study highlights the need for large-scale validation of cTfh cell frequency and function in PWH.</p> Clinical trial number <p>Not applicable.</p>

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Dysfunction of circulating follicular helper T cells in people living with HIV who are HBV small surface protein antibody (HBsAb)-negative despite HBV vaccination

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月11日

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  • Ayako Sedohara,
  • Yoshiaki Kanno,
  • Keiko Arai,
  • Kotaro Arizono,
  • Michiko Koga,
  • Fumio Nakahara,
  • Makoto Saito,
  • Eisuke Adachi,
  • Hiroshi Yotsuyanagi

摘要

Background

The seroconversion rate after hepatitis B virus (HBV) vaccination in people living with human immunodeficiency virus (HIV) is reportedly lower than that in non-HIV controls. Follicular helper T (Tfh) cells play a central role in humoral immunity, and IL-21 secreted by Tfh cells is essential for B cells to differentiate into plasma cells. This study investigated the frequency and function of circulating Tfh (cTfh) cells isolated from people living with HIV (PWH) who are negative for hepatitis B virus (HBV) surface antigen (HBsAb−) in a small cohort of PWH who received HBV vaccination.

Case presentation

The frequency of cTfh cells in HBsAb− PWH (HBsAb levels less than 10 mIU/mL) was the same as that in non-HIV controls and HBsAb positive (HBsAb+) PWH, who maintained HBsAb at 10 mIU/mL for at least 1 year after receiving three doses of the HBV vaccine. However, after immune stimulation with anti-CD3/CD28 antibodies, the frequency of cTfh cells in the non-HIV controls and HBsAb+ PWH increased, whereas the frequency of cTfh cells in the HBsAb− PWH tended to be more gradual. cTfh17-like and cTfh2-like cells, subsets of cTfh cells, are involved in humoral immunity, and PD-1 regulates the function of these cells in the germinal center. The frequencies of PD-1+ cTfh17-like and cTfh2-like cells at baseline did not differ significantly among the three groups. However, HBsAb− PWH had a lower frequency of PD-1+ cTfh17-like cells after immune stimulation than non-HIV controls did. The frequencies of PD-1+ cTfh17-like cells and cTfh2-like cells with high PD-1 expression were significantly lower in HBsAb− PWH than in non-HIV controls. Furthermore, the production of IL-21, which is essential for plasma cell differentiation, tended to be lower in HBsAb− PWH than in non-HIV controls or HBsAb+ PWH.

Conclusions

cTfh cells isolated from HBsAb− PWH may be unable to produce sufficient IL-21 after immune stimulation. This study is the first to suggest that cTfh cells may not function adequately in some PWH. This study highlights the need for large-scale validation of cTfh cell frequency and function in PWH.

Clinical trial number

Not applicable.