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. 2025 Feb;39(2):499-502.
doi: 10.1038/s41375-024-02463-9. Epub 2024 Nov 22.

CLL crosstalk with naïve T cells enhances the differentiation of IL-22-producing T cells and CLL -cell survival

Gerardo Ferrer  1   2   3 , Florencia Palacios  4   5 , Pui Yan Chiu  6 , Kelly Wong  4 , Alberto Bueno-Costa  7   8 , Jacqueline C Barrientos  4   9   10 , Jonathan E Kolitz  4   9   10 , Steven L Allen  4   9   10 , Kanti R Rai  4   9   10 , Shih-Shih Chen  4 , Barbara Sherry  6   10   11 , Nicholas Chiorazzi  4   9   10   11
Affiliations

CLL crosstalk with naïve T cells enhances the differentiation of IL-22-producing T cells and CLL -cell survival

Gerardo Ferrer et al. Leukemia. 2025 Feb.
No abstract available

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Increased numbers of Th22 and Tc22 cells in peripheral blood of CLL patients correlates with shorter TTFT.
A Flow cytometry marker and gating strategies to identify IL-22-producing T cells. B, C Absolute numbers of circulating CD3+, CD4+, CD8+, Th22+, and Tc22+ cells from patients with CLL and gender- and age-matched healthy controls (HC). D Absolute counts of circulating Th22+ and Tc22+ cells from patients who required treatment vs. those who did not. E CLL patients were dichotomized into High and Low count subsets based on the numbers of IL-22-producing T cells using the Maxstat package for R-2.8.0. TTFT curves were calculated by the Kaplan-Meier method, and comparisons between groups were performed by the log-rank test. P-values: * < 0.05, ** < 0.01, and ***< 0.001.
Fig. 2
Fig. 2. CLL cells enhance naïve T-cell differentiation to Th22 cells, and IL-22 augments CLL-cell survival by microenvironmental influences.
A, B FACS-isolated naïve CD4+ T cells (CD3+CD4+CD45RO-CD62L+; Tn) from PBMCs of 20 CLL patients and 10 HC were stimulated in vitro with anti-CD3/CD28 beads + IL2 for 6 days, and then the percentages of IL-22 cytokine-producing cells were measured by flow cytometry. C Supernatants from cultures of patient T cells and patient T + autologous CLL B cells were analyzed for the levels of soluble IL-22 by ELISA. D Levels of IL-22 in the supernatant of CD4+ Tn (n = 5) cultured in direct contact with CLL B cells or separated by a 0.4 µm pore membrane in a Transwell plate. E, G CLL-cell viability in 12 patient samples was evaluated in vitro by flow cytometry using FxCycle™ Violet and Annexin V staining in the presence or absence of recombinant human IL-22 (0.2–2 ug/ml) for 96 hours. F IL-22RA1 gene expression in samples from 32 purified normal B cells from HC and 188 CLL B cells (GSE50006). The dotted line indicates the trustable noise/signal threshold. H Percentage of IL-22RA1+ cells within PBMCs monocytes (CD14+ cells) and T cells (CD3+ cells) populations from five healthy controls and ten CLL patients evaluated by flow cytometry. P-values: * < 0.05, ** < 0.01, and ***< 0.001.
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