Mitochondrial basis for immune deficiency. Evidence from purine nucleoside phosphorylase-deficient mice.


Journal Article

We generated purine nucleoside phosphorylase (PNP)-deficient mice to gain insight into the mechanism of immune deficiency disease associated with PNP deficiency in humans. Similar to the human disease, PNP deficiency in mice causes an immunodeficiency that affects T lymphocytes more severely than B lymphocytes. PNP knockout mice exhibit impaired thymocyte differentiation, reduced mitogenic and allogeneic responses, and decreased numbers of maturing thymocytes and peripheral T cells. T lymphocytes of PNP-deficient mice exhibit increased apoptosis in vivo and higher sensitivity to gamma irradiation in vitro. We propose that the immune deficiency in PNP deficiency is a result of inhibition of mitochondrial DNA repair due to the accumulation of dGTP in the mitochondria. The end result is increased sensitivity of T cells to spontaneous mitochondrial DNA damage, leading to T cell depletion by apoptosis.

Full Text

Duke Authors

Cited Authors

  • Arpaia, E; Benveniste, P; Di Cristofano, A; Gu, Y; Dalal, I; Kelly, S; Hershfield, M; Pandolfi, PP; Roifman, CM; Cohen, A

Published Date

  • June 19, 2000

Published In

Volume / Issue

  • 191 / 12

Start / End Page

  • 2197 - 2208

PubMed ID

  • 10859343

Pubmed Central ID

  • 10859343

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.191.12.2197


  • eng

Conference Location

  • United States