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Role of tumor suppressor TSC1 in regulating antigen-specific primary and memory CD8 T cell responses to bacterial infection.

Publication ,  Journal Article
Krishna, S; Yang, J; Wang, H; Qiu, Y; Zhong, X-P
Published in: Infect Immun
July 2014

The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) integrates various environmental cues such as the presence of antigen, inflammation, and nutrients to regulate T cell growth, metabolism, and function. The tuberous sclerosis 1 (TSC1)/TSC2 complex negatively regulates the activity of an mTOR-containing multiprotein complex called mTOR complex 1. Recent studies have revealed an essential cell-intrinsic role for TSC1 in T cell survival, quiescence, and mitochondrial homeostasis. Given the emerging role of mTOR activity in the regulation of the quantity and quality of CD8 T cell responses, in this study, we examine the role of its suppressor, TSC1, in the regulation of antigen-specific primary and memory CD8 T cell responses to bacterial infection. Using an established model system of transgenic CD8 cell adoptive transfer and challenge with Listeria monocytogenes expressing a cognate antigen, we found that TSC1 deficiency impairs antigen-specific CD8 T cell responses, resulting in weak expansion, exaggerated contraction, and poor memory generation. Poor expansion of TSC1-deficient cells was associated with defects in survival and proliferation in vivo, while enhanced contraction was correlated with an increased ratio of short-lived effectors to memory precursors in the effector cell population. This perturbation of effector-memory differentiation was concomitant with decreased expression of eomesodermin among activated TSC1 knockout cells. Upon competitive adoptive transfer with wild-type counterparts and antigen rechallenge, TSC1-deficient memory cells showed moderate defects in expansion but not cytokine production. Taken together, these findings provide direct evidence of a CD8 T cell-intrinsic role for TSC1 in the regulation of antigen-specific primary and memory responses.

Duke Scholars

Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

July 2014

Volume

82

Issue

7

Start / End Page

3045 / 3057

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tuberous Sclerosis Complex 1 Protein
  • Spleen
  • Ovalbumin
  • Microbiology
  • Mice, Knockout
  • Mice
  • Listeriosis
  • Listeria monocytogenes
  • Gene Expression Regulation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Krishna, S., Yang, J., Wang, H., Qiu, Y., & Zhong, X.-P. (2014). Role of tumor suppressor TSC1 in regulating antigen-specific primary and memory CD8 T cell responses to bacterial infection. Infect Immun, 82(7), 3045–3057. https://doi.org/10.1128/IAI.01816-14
Krishna, Sruti, Jialong Yang, Hongxia Wang, Yurong Qiu, and Xiao-Ping Zhong. “Role of tumor suppressor TSC1 in regulating antigen-specific primary and memory CD8 T cell responses to bacterial infection.Infect Immun 82, no. 7 (July 2014): 3045–57. https://doi.org/10.1128/IAI.01816-14.
Krishna S, Yang J, Wang H, Qiu Y, Zhong X-P. Role of tumor suppressor TSC1 in regulating antigen-specific primary and memory CD8 T cell responses to bacterial infection. Infect Immun. 2014 Jul;82(7):3045–57.
Krishna, Sruti, et al. “Role of tumor suppressor TSC1 in regulating antigen-specific primary and memory CD8 T cell responses to bacterial infection.Infect Immun, vol. 82, no. 7, July 2014, pp. 3045–57. Pubmed, doi:10.1128/IAI.01816-14.
Krishna S, Yang J, Wang H, Qiu Y, Zhong X-P. Role of tumor suppressor TSC1 in regulating antigen-specific primary and memory CD8 T cell responses to bacterial infection. Infect Immun. 2014 Jul;82(7):3045–3057.

Published In

Infect Immun

DOI

EISSN

1098-5522

Publication Date

July 2014

Volume

82

Issue

7

Start / End Page

3045 / 3057

Location

United States

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tuberous Sclerosis Complex 1 Protein
  • Spleen
  • Ovalbumin
  • Microbiology
  • Mice, Knockout
  • Mice
  • Listeriosis
  • Listeria monocytogenes
  • Gene Expression Regulation