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Isolation and Activation of Murine Lymphocytes
08:08

Isolation and Activation of Murine Lymphocytes

Published on: October 30, 2016

Activation of leukemic large granular lymphocytes by interleukin-2 via the p75 interleukin-2 receptor

H J Yoon1, K Sugamura, T P Loughran

  • 1Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.

Leukemia
|December 1, 1990
PubMed

Insights

Interleukin-2 (IL-2) activates leukemic large granular lymphocytes (LGL) through p75 IL-2 receptors. Blocking these receptors inhibits LGL proliferation and cytotoxic functions, revealing a key mechanism in LGL leukemia.

Area of Science:

  • Immunology
  • Hematology
  • Cell Biology

Background:

  • Large granular lymphocyte (LGL) leukemia is a rare hematologic malignancy.
  • Interleukin-2 (IL-2) plays a role in lymphocyte activation and proliferation.
  • The IL-2 receptor is composed of multiple subunits, including p55 (alpha) and p75 (beta).

Purpose of the Study:

  • To investigate the role of IL-2 receptor subunits in the activation of leukemic CD3+ large granular lymphocytes (LGL).
  • To determine which IL-2 receptor subunit is responsible for mediating IL-2-induced proliferation and cytotoxic functions in LGL leukemia.

Main Methods:

  • Peripheral blood mononuclear cells from patients with CD3+ LGL leukemia were isolated.
  • Cells were activated with recombinant IL-2.
  • Monoclonal antibodies against IL-2 receptor subunits (anti-p75 and anti-p55) were used to block receptor function.
  • Cell proliferation and cytotoxic activity were measured.
  • Cell sorting experiments were performed to confirm the target cells.

Main Results:

  • IL-2 induced both proliferative and cytotoxic functions in leukemic LGL.
  • The addition of anti-p75 IL-2 receptor monoclonal antibody blocked IL-2-induced functions.
  • The addition of anti-p55 IL-2 receptor monoclonal antibody did not affect IL-2-induced functions.
  • Sorting experiments confirmed that the anti-p75 antibody acted directly on leukemic LGL.

Conclusions:

  • Leukemic LGL constitutively express functional p75 IL-2 receptors.
  • The p75 IL-2 receptor subunit is critical for IL-2-mediated activation of leukemic LGL.
  • This finding suggests a potential therapeutic target for LGL leukemia by blocking the p75 IL-2 receptor.

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