Suppression of CD4+ T lymphocyte activation in vitro and experimental encephalomyelitis in vivo by the phosphatidyl inositol 3-kinase inhibitor PIK-75 Academic Article


  • International Journal of Immunopathology and Pharmacology


  • Class IA phosphatidyl inositol-3 kinases (PI3-K) are important targets in cancer therapy and are essential to immune responses, particularly through costimulation by CD28 and ICOS. Thus, small PI3-K inhibitors are likely candidates to immune intervention. PIK-75 is an efficient inhibitor of the PI3-K p110α catalytic subunits that suppresses tumor growth, and its effects on immune and autoimmune responses should be studied. Here, we describe the effect of PIK-75 on different immune parameters in vitro and in vivo. PIK-75 at concentrations commonly used in vitro (≥0.1 μM) inhibited T and B cell activation by Concanavalin A and LPS, respectively, and survival of non-stimulated spleen cells. In naive CD4+ T lymphocytes, PIK-75 induced apoptosis of resting or activated cells that was prevented by caspase inhibitors. At low nanomolar concentrations (≤10 nM), PIK-75 inhibited naive CD4+ T cell proliferation, and IL-2 and IFN-γ production induced by anti-CD3 plus anti-CD28. In activated CD4+ T blasts costimulated by ICOS, PIK-75 (≤10 nM) inhibited IFN-γ, IL-17A, or IL-21 secretion. Furthermore, PIK-75 (20 mg/kg p.o.) suppressed clinical symptoms in ongoing experimental autoimmune encephalomyelitis (EAE) and inhibited MOG-specific responses in vitro. Thus, PIK-75 is an efficient suppressor of EAE, modulating lymphocyte function and survival.

publication date

  • 2014-1-1


  • 27


  • Apoptosis
  • Autoimmune Experimental Encephalomyelitis
  • Autoimmunity
  • B-Lymphocytes
  • Caspase Inhibitors
  • Catalytic Domain
  • Cell Proliferation
  • Concanavalin A
  • Encephalomyelitis
  • Growth
  • In Vitro Techniques
  • Interleukin-17
  • Interleukin-2
  • Lymphocyte Activation
  • Lymphocytes
  • Neoplasms
  • PIK 75
  • Phosphatidylinositols
  • Phosphotransferases
  • Spleen
  • T-Lymphocytes
  • Therapeutics
  • interleukin-21

International Standard Serial Number (ISSN)

  • 0394-6320

number of pages

  • 15

start page

  • 53

end page

  • 67