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Interleukin 2 induces the expression of CD45RO and the memory phenotype by CD45RA+ peripheral blood lymphocytes

M D Roth1

  • 1Department of Medicine, University of California, Los Angeles School of Medicine 90024.

The Journal of Experimental Medicine
|March 1, 1994
PubMed

Insights

Interleukin 2 (IL-2) drives naive T cells (CD45RA+) to become memory T cells (CD45RO+). This cytokine also influences T cell adhesion molecule expression and is crucial for CD45RO expression following T cell receptor stimulation.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Naive T cells (CD45RA+) differentiate into memory T cells (CD45RO+) upon activation, a process typically induced by antigens or mitogens.
  • The role of cytokines, particularly interleukin 2 (IL-2), in mediating this naive-to-memory T cell transition remains incompletely understood.
  • T cell activation involves changes in the expression of cell surface molecules, including adhesion molecules, which are critical for immune cell function.

Purpose of the Study:

  • To investigate the role of interleukin 2 (IL-2) in the in vitro conversion of naive T cells (CD45RA+/CD45RO-) to a memory phenotype (CD45RA-/CD45RO+).
  • To examine the impact of IL-2 on the expression of adhesion molecules during T cell differentiation.
  • To determine the necessity of endogenous IL-2 for CD45RO expression following T cell receptor/CD3 complex stimulation.

Main Methods:

  • Purified peripheral blood lymphocytes (PBL) expressing CD45RA+/CD45RO- were cultured in vitro with IL-2.
  • Flow cytometry was used to analyze the expression of CD45 isoforms (CD45RA and CD45RO) and adhesion molecules (CD2, CD11a, CDw29, Leu-8/LAM-1).
  • T cell activation was induced using immobilized anti-CD3 in the presence of neutralizing anti-IL-2 antibodies and/or cyclosporin A.

Main Results:

  • In vitro exposure to IL-2 induced the conversion of CD45RA+/CD45RO- T cells to the CD45RA-/CD45RO+ memory phenotype.
  • This conversion was observed in both CD3+ and CD3-/CD56+ lymphocyte subsets, occurring more rapidly in the latter.
  • IL-2 treatment led to increased expression of CD2, CD11a, and CDw29, and decreased expression of Leu-8 (LAM-1), while lymphocytes remaining CD45RA+/CD45RO- showed no change in adhesion molecule profiles.
  • Neutralizing anti-IL-2 antibodies and cyclosporin A significantly reduced IL-2-dependent CD45RO expression during anti-CD3 stimulation, with cyclosporin A's effect being reversible by exogenous IL-2.

Conclusions:

  • Interleukin 2 (IL-2) is a key cytokine that promotes the differentiation of naive T cells (CD45RA+) into cells expressing the memory phenotype (CD45RO+).
  • IL-2 influences the expression of T cell adhesion molecules during this differentiation process.
  • Endogenous IL-2 plays a critical role in mediating CD45RO expression subsequent to T cell receptor/CD3 complex activation.

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