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

Alicia M. Vaca, Nikolaos Ioannou, Mariela Sivina, Elisavet Vlachonikola, Karen Clise-Dwyer, Ekaterina Kim, Dan Li, Qing Ma, Alessandra Ferrajoli, Zeev Estrov, William G. Wierda, Piers E.M. Patten, Alan G. Ramsay, Jan A. Burger

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalLeukemia
DOIs
StateAccepted/In press - 2022

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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