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Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus.

Publication ,  Journal Article
Palendira, U; Low, C; Bell, AI; Ma, CS; Abbott, RJM; Phan, TG; Riminton, DS; Choo, S; Smart, JM; Lougaris, V; Giliani, S; Buckley, RH ...
Published in: J Exp Med
May 7, 2012

Patients with the primary immunodeficiency X-linked lymphoproliferative disease (XLP), which is caused by mutations in SH2D1A, are highly susceptible to Epstein-Barr virus (EBV) infection. Nonetheless, some XLP patients demonstrate less severe clinical manifestations after primary infection. SH2D1A encodes the adaptor molecule SLAM-associated protein (SAP), which is expressed in T and natural killer cells and is required for cytotoxicity against B cells, the reservoir for EBV. It is not known why the clinical presentation of XLP is so variable. In this study, we report for the first time the occurrence of somatic reversion in XLP. Reverted SAP-expressing cells resided exclusively within the CD8(+) T cell subset, displayed a CD45RA(-)CCR7(-) effector memory phenotype, and were maintained at a stable level over time. Importantly, revertant CD8(+) SAP(+) T cells, but not SAP(-) cells, proliferated in response to EBV and killed EBV-infected B cells. As somatic reversion correlated with EBV infection, we propose that the virus exerts a selective pressure on the reverted cells, resulting in their expansion in vivo and host protection against ongoing infection.

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Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

May 7, 2012

Volume

209

Issue

5

Start / End Page

913 / 924

Location

United States

Related Subject Headings

  • Viral Load
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Sequence Analysis, DNA
  • Mutation
  • Molecular Sequence Data
  • Lymphoproliferative Disorders
  • Intracellular Signaling Peptides and Proteins
  • Immunology
  • Immunologic Memory
  • Humans
 

Citation

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Palendira, U., Low, C., Bell, A. I., Ma, C. S., Abbott, R. J. M., Phan, T. G., … Tangye, S. G. (2012). Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus. J Exp Med, 209(5), 913–924. https://doi.org/10.1084/jem.20112391
Palendira, Umaimainthan, Carol Low, Andrew I. Bell, Cindy S. Ma, Rachel J. M. Abbott, Tri Giang Phan, D Sean Riminton, et al. “Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus.J Exp Med 209, no. 5 (May 7, 2012): 913–24. https://doi.org/10.1084/jem.20112391.
Palendira, Umaimainthan, et al. “Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus.J Exp Med, vol. 209, no. 5, May 2012, pp. 913–24. Pubmed, doi:10.1084/jem.20112391.
Palendira U, Low C, Bell AI, Ma CS, Abbott RJM, Phan TG, Riminton DS, Choo S, Smart JM, Lougaris V, Giliani S, Buckley RH, Grimbacher B, Alvaro F, Klion AD, Nichols KE, Adelstein S, Rickinson AB, Tangye SG. Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus. J Exp Med. 2012 May 7;209(5):913–924.

Published In

J Exp Med

DOI

EISSN

1540-9538

Publication Date

May 7, 2012

Volume

209

Issue

5

Start / End Page

913 / 924

Location

United States

Related Subject Headings

  • Viral Load
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Sequence Analysis, DNA
  • Mutation
  • Molecular Sequence Data
  • Lymphoproliferative Disorders
  • Intracellular Signaling Peptides and Proteins
  • Immunology
  • Immunologic Memory
  • Humans