Peripheral helper T (Tph) and follicular helper T (Tfh) cells are key regulators of B cell differentiation and antibody production, making them promising targets for autoimmune disease treatment. However, their differentiation mechanisms differ significantly between humans and mice, limiting drug validation in mouse models. Here, we present a simple and effective method for in vivo proliferation of human Tph/Tfh and B cells. We discovered that after depleting CD8+ T cells of human peripheral blood mononuclear cell–transferred immunodeficient mice (CD8TΔhPBMC mice), human Tph/Tfh cells and B cells proliferated markedly in the spleen compared with those in human PBMC–transferred immunodeficient mice (hPBMC mice). Transcriptome analysis confirmed proliferating cells’ close resemblance to human Tph/Tfh cells. Furthermore, multicolor flow cytometry revealed CXCL13+ Tph cells infiltrating Sjögren’s syndrome–associated (SjS-associated) organs, such as salivary glands. Single-cell RNA sequencing identified IL-21+CXCL13+IFN-γ+ICOS+TIGIT+GPR56+ Tph cells in the salivary glands. These findings are consistent with reduced saliva volume and elevated SjS markers, such as anti-SSA antibody, in these mice, which were both ameliorated by immunosuppressants. In vitro, CD8+ T cells from hPBMC mice induced B cell apoptosis and inhibited Tph/Tfh differentiation. This model advances understanding of human Tph/Tfh cell biology and offers a valuable platform for studying SjS and therapeutic targets.
Mariam Piruzyan, Sota Fujimori, Ryota Sato, Yuki Imura, Sachiko Mochiduki, Kana Takemoto, Akiko Nishidate, Yuzo Koda
Usage data is cumulative from November 2025 through December 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 769 | 24 |
| 183 | 3 | |
| Figure | 205 | 0 |
| Supplemental data | 60 | 0 |
| Citation downloads | 37 | 0 |
| Totals | 1,254 | 27 |
| Total Views | 1,281 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.