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Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection.

Publication ,  Journal Article
Crosby, EJ; Goldschmidt, MH; Wherry, EJ; Scott, P
Published in: Plos Pathog
February 2014

One of the hallmarks of adaptive immunity is the development of a long-term pathogen specific memory response. While persistent memory T cells certainly impact the immune response during a secondary challenge, their role in unrelated infections is less clear. To address this issue, we utilized lymphocytic choriomeningitis virus (LCMV) and Listeria monocytogenes immune mice to investigate whether bystander memory T cells influence Leishmania major infection. Despite similar parasite burdens, LCMV and Listeria immune mice exhibited a significant increase in leishmanial lesion size compared to mice infected with L. major alone. This increased lesion size was due to a severe inflammatory response, consisting not only of monocytes and neutrophils, but also significantly more CD8 T cells. Many of the CD8 T cells were LCMV specific and expressed gzmB and NKG2D, but unexpectedly expressed very little IFN-γ. Moreover, if CD8 T cells were depleted in LCMV immune mice prior to challenge with L. major, the increase in lesion size was lost. Strikingly, treating with NKG2D blocking antibodies abrogated the increased immunopathology observed in LCMV immune mice, showing that NKG2D engagement on LCMV specific memory CD8 T cells was required for the observed phenotype. These results indicate that bystander memory CD8 T cells can participate in an unrelated immune response and induce immunopathology through an NKG2D dependent mechanism without providing increased protection.

Duke Scholars

Published In

Plos Pathog

DOI

EISSN

1553-7374

Publication Date

February 2014

Volume

10

Issue

2

Start / End Page

e1003970

Location

United States

Related Subject Headings

  • Virology
  • NK Cell Lectin-Like Receptor Subfamily K
  • Mice, Inbred C57BL
  • Mice
  • Lymphocytic choriomeningitis virus
  • Lymphocytic Choriomeningitis
  • Lymphocyte Activation
  • Leishmaniasis, Cutaneous
  • Leishmania major
  • Immunologic Memory
 

Citation

APA
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ICMJE
MLA
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Crosby, E. J., Goldschmidt, M. H., Wherry, E. J., & Scott, P. (2014). Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection. Plos Pathog, 10(2), e1003970. https://doi.org/10.1371/journal.ppat.1003970
Crosby, Erika J., Michael H. Goldschmidt, E John Wherry, and Phillip Scott. “Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection.Plos Pathog 10, no. 2 (February 2014): e1003970. https://doi.org/10.1371/journal.ppat.1003970.
Crosby EJ, Goldschmidt MH, Wherry EJ, Scott P. Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection. Plos Pathog. 2014 Feb;10(2):e1003970.
Crosby, Erika J., et al. “Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection.Plos Pathog, vol. 10, no. 2, Feb. 2014, p. e1003970. Pubmed, doi:10.1371/journal.ppat.1003970.
Crosby EJ, Goldschmidt MH, Wherry EJ, Scott P. Engagement of NKG2D on bystander memory CD8 T cells promotes increased immunopathology following Leishmania major infection. Plos Pathog. 2014 Feb;10(2):e1003970.

Published In

Plos Pathog

DOI

EISSN

1553-7374

Publication Date

February 2014

Volume

10

Issue

2

Start / End Page

e1003970

Location

United States

Related Subject Headings

  • Virology
  • NK Cell Lectin-Like Receptor Subfamily K
  • Mice, Inbred C57BL
  • Mice
  • Lymphocytic choriomeningitis virus
  • Lymphocytic Choriomeningitis
  • Lymphocyte Activation
  • Leishmaniasis, Cutaneous
  • Leishmania major
  • Immunologic Memory