4.7 Article

Activation and expansion of T-follicular helper cells in chronic lymphocytic leukemia nurselike cell co-cultures

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LEUKEMIA
卷 36, 期 5, 页码 1324-1335

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SPRINGERNATURE
DOI: 10.1038/s41375-022-01519-y

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资金

  1. NCI [P30CA016672]
  2. MRC [MR/T005106/1]
  3. ERA-NET on Translational Cancer Research (TRANSCAN-2) [5041673]
  4. CLL Global Research Foundation
  5. MRC [MR/T005106/1] Funding Source: UKRI

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This study reveals the interaction and clonal expansion mechanism between chronic lymphocytic leukemia (CLL) cells and T-cell subsets, indicating the interaction of Tfh cells with proliferating leukemia cells and providing new avenues for treating CLL.
Interactions between chronic lymphocytic leukemia (CLL) cells and T-cell subsets in the lymph node microenvironment are thought to play a central role in disease biology. To study these interactions in a model of the CLL lymph node microenvironment, we characterized T-cell subsets in CLL nurselike cell (NLC) co-cultures. We focused on T-follicular helper (Tfh) cells, which are characterized by CXCR5 expression and localization to B-cell follicles. In co-cultures from 28 different CLL patients, we detected an expansion of Tfh cells based on PD-1, BCL6, and ICOS expression, with increased IL-21 and downmodulated CD40L surface expression. Regulatory T cells (Treg), which promote immune tolerance, also expanded in NLC co-cultures. T-cell receptor (TR) gene repertoire analyses confirmed the clonal expansion of CD4(+) T cells, with an enrichment of TR clonotypes commonly expanded also in primary CLL samples. Multicolor confocal microscopy revealed that Tfh, but not Treg co-localize with proliferating CLL cells in CLL lymph node sections. Collectively, these data provide new insight into the cellular and molecular cross-talk between CLL and T-cell subsets, resulting in clonal expansion of T-helper cells and interaction of Tfh cells with proliferating CLL cells which may open new avenues for therapeutic targeting.

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