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

Enrico Arpaia, Patricia Benveniste, Antonio Di Cristofano, Yiping Gu, Ilan Dalal, Susan Kelly, Michael Hershfield, Pier Paolo Pandolfi, Chaim M. Roifman, Amos Cohen

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


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 oft cells to spontaneous mitochondrial DNA damage, leading to T cell depletion by apoptosis.

Original languageEnglish (US)
Pages (from-to)2197-2207
Number of pages11
JournalJournal of Experimental Medicine
Issue number12
StatePublished - Jun 19 2000
Externally publishedYes


  • Apoptosis
  • Immune deficiency
  • Mitochondria
  • Purine metabolism
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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