Interleukin 2 induction of pore-forming protein gene expression in human peripheral blood CD8+ T cells

J Exp Med. 1990 Apr 1;171(4):1269-81. doi: 10.1084/jem.171.4.1269.

Abstract

Our studies have analyzed pore-forming protein (PFP) mRNA expression in resting and stimulated human peripheral blood CD3- large granular lymphocytes (LGL), CD3+ T cells, and their CD4+ or CD8+ subsets. Signals that stimulate T cells to develop cytotoxic activity (i.e., IL-2 or OKT-3 mAb) led to the induction of PFP mRNA in T cells. The data indicated that IL-2 directly increased PFP mRNA in the CD8+ subset of T cells, in the absence of new DNA or protein synthesis. Abrogation of IL-2-induced PFP mRNA expression and cytotoxic potential of T cells by the anti-p75 IL-2 receptor mAb suggested that low numbers of p75 IL-2 receptors on CD8+ T cells were capable of transducing signals responsible for these IL-2-induced effects. The induction of T cell PFP mRNA via CD3, using OKT-3 mAb, was less rapid but greater than that caused by IL-2; however, a combination of PMA and ionomycin, which bypasses crosslinking of the TCR/CD3 complex, could not mimic this increase in PFP mRNA levels in T cells. The role of second messenger systems in regulating PFP mRNA expression remains to be determined. In contrast, high constitutive PFP mRNA expression was observed in CD3- LGL and these mRNA levels could not be enhanced by stimulation with IL-2. The cytotoxic potential of peripheral blood T cells and LGL induced in response to IL-2 correlated with IL-2-induced PFP mRNA levels in these cells and was consistent with PFP being one of several important molecules involved in the effector function of cytotoxic lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • Antigens, CD / analysis
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • CD3 Complex
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Gene Expression / drug effects*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / pharmacology*
  • Kinetics
  • Lymphocyte Activation
  • Membrane Glycoproteins*
  • Membrane Proteins / genetics*
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • RNA / blood
  • RNA / genetics
  • RNA / isolation & purification
  • RNA, Messenger / genetics
  • Receptors, Antigen, T-Cell / analysis
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Interleukin-2
  • Membrane Glycoproteins
  • Membrane Proteins
  • Pore Forming Cytotoxic Proteins
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • Perforin
  • RNA
  • Interferon-gamma