Mitochondrial basis for immune deficiency: Evidence from purine nucleoside phosphorylase-deficient mice Journal Article
| Authors: | Arpaia, E.; Benveniste, P.; Di Cristofano, A.; Gu, Y.; Dalal, I.; Kelly, S.; Hershfield, M.; Pandolfi, P. P.; Roifman, C. M.; Cohen, A. |
| Article Title: | Mitochondrial basis for immune deficiency: Evidence from purine nucleoside phosphorylase-deficient mice |
| Abstract: | 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. |
| Keywords: | pathogenesis; nonhuman; t lymphocyte; cd8-positive t-lymphocytes; t-lymphocytes; animal cell; mouse; animals; mice; mice, knockout; dna repair; protein bcl 2; apoptosis; cell differentiation; thymus gland; cd4-positive t-lymphocytes; radiosensitivity; cytotoxicity, immunologic; t-lymphocyte subsets; immune deficiency; mitochondria; thymocyte; mitochondrion; severe combined immunodeficiency; knockout mouse; purine-nucleoside phosphorylase; purine nucleoside phosphorylase; priority journal; article; purine metabolism; deoxyguanine nucleotides |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 191 |
| Issue: | 12 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2000-06-19 |
| Start Page: | 2197 |
| End Page: | 2207 |
| Language: | English |
| DOI: | 10.1084/jem.191.12.2197 |
| PUBMED: | 10859343 |
| PROVIDER: | scopus |
| PMCID: | PMC2193200 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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