Adenosine monophosphate deaminase 3 null mutation causes reduction of naive T cells in mouse peripheral blood

Xiaoming Zhan, Xue Zhong, Jin Huk Choi, Lijing Su, Jianhui Wang, Evan Nair-Gill, Priscilla Anderton, Xiaohong Li, Miao Tang, Jamie Russell, Sara Ludwig, Thomas Gallagher, Bruce Beutler

Research output: Contribution to journalArticlepeer-review

Abstract

Adenosinemonophosphate deaminase 3 (Ampd3) encodes the erythrocyte isoform of the adenosine monophosphate (AMP) deaminase gene family. Mutations in this gene have been reported in humans, leading to autosomal-recessive erythrocyte AMP deaminase deficiency. However, the mutation is considered clinically asymptomatic. Using N-ethyl-N-nitrosourea mutagenesis to find mutations that affect peripheral lymphocyte populations, we identified 5 Ampd3 mutations (Ampd3guangdong, Ampd3carson, Ampd3penasco, Ampd3taos, and Ampd3commanche) that strongly correlated with a reduction in naive CD4+ T and naive CD8+ T-cell populations. Causation was confirmed by targeted ablation of Ampd3. Knockout mice had reduced frequencies of CD62LhiCD44lo CD4+ naive and CD8+ naive T cells. Interestingly, these phenotypes were restricted to T cells circulating in peripheral blood and were not seen in T cells from secondary lymphoid organs (lymph nodes and spleen). We found that reduction of naive T cells in the peripheral blood of Ampd3-/- mice was caused by T-cell-extrinsic factor(s), which we hypothesize to be elevated levels of adenosine triphosphate released by Ampd3-deficient erythrocytes. These findings provide an example in which disruption of an erythrocyte-specific protein can affect the physiological status of lymphocytes in peripheral blood.

Original languageEnglish (US)
Pages (from-to)3594-3605
Number of pages12
JournalBlood Advances
Volume4
Issue number15
DOIs
StatePublished - Aug 11 2020

ASJC Scopus subject areas

  • Hematology

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