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July 16, 2021Blood AdvancesOpen Access

CD4+ T cells sustain aggressive chronic lymphocytic leukemia in Eμ-TCL1 mice through a CD40L-independent mechanism

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Authors

MGMatteo GrioniABArianna BreviECElena Cattaneo

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Overview

Preclinical animal study reveals CD4+ T cells promote chronic lymphocytic leukemia progression via CD40-independent pathways while CD8+ T cells restrain it, indicating novel therapeutic targets.

Key Points

  • To determine the in vivo role and molecular mechanism of CD4+ and CD8+ T lymphocytes and the CD40L/CD40 axis in sustaining aggressive chronic lymphocytic leukemia progression.
  • Generated genetically modified Eμ-TCL1 mouse models lacking CD4+ T cells (TCL1+/+AB0), CD40 (TCL1+/+CD40-/-), or CD8+ T cells (TCL1+/+TAP-/-).
  • Monitored disease progression using flow cytometry and immunohistochemical analyses.
  • Conducted adoptive transfer of leukemic cells into mice lacking CD4+ T cells or CD40L, or into wild-type mice treated with CD4-depleting or CD40/CD40L-blocking antibodies.
  • Leukemic clones failed to proliferate in mice lacking or depleted of CD4+ T cells, demonstrating CD4+ T cells are required for leukemia development.
  • CD8+ T-cell deficiency in TCL1+/+TAP-/- mice accelerated disease progression, demonstrating an endogenous antitumor effect.
  • Leukemic clones efficiently proliferated in CD40L-/- hosts, TCL1+/+CD40-/- mice, and mice treated with CD40-blocking antibodies, confirming leukemic progression relies on CD40-independent, noncognate CD4+ T-cell interactions.

Cite This Study

Grioni et al. (2021) studied this question.

synapsesocial.com/papers/6a9032c82a22b8e8a92da1d4https://doi.org/10.1182/bloodadvances.2020003795
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