Sprouty-2 regulates HIV-specific T cell polyfunctionality

Yen Ling Chiu, Liang Shan, Hailiang Huang, Carl Haupt, Catherine Bessell, David H. Canaday, Hao Zhang, Ya Chi Ho, Jonathan Powell, Mathias Oelke, Joseph Bernard Margolick, Joel N Blankson, Diane Griffin, Jonathan P Schneck

Research output: Contribution to journalArticle

Abstract

The ability of individual T cells to perform multiple effector functions is crucial for protective immunity against viruses and cancer. This polyfunctionality is frequently lost during chronic infections; however, the molecular mechanisms driving T cell polyfunctionality are poorly understood. We found that human T cells stimulated by a high concentration of antigen lacked polyfunctionality and expressed a transcription profile similar to that of exhausted T cells. One specific pathway implicated by the transcription profile in control of T cell polyfunctionality was the MAPK/ERK pathway. This pathway was altered in response to different antigen concentrations, and polyfunctionality correlated with upregulation of phosphorylated ERK. T cells that were stimulated with a high concentration of antigen upregulated sprouty-2 (SPRY2), a negative regulator of the MAPK/ERK pathway. The clinical relevance of SPRY2 was confirmed by examining SPRY2 expression in HIV-specific T cells, where high levels of SPRY2 were seen in HIV-specific T cells and inhibition of SPRY2 expression enhanced the HIV-specific polyfunctional response independently of the PD-1 pathway. Our findings indicate that increased SPRY2 expression during chronic viral infection reduces T cell polyfunctionality and identify SPRY2 as a potential target for immunotherapy.

Original languageEnglish (US)
Pages (from-to)198-208
Number of pages11
JournalJournal of Clinical Investigation
Volume124
Issue number1
DOIs
StatePublished - Jan 2 2014

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HIV-2
T-Lymphocytes
MAP Kinase Signaling System
HIV
Antigens
Virus Diseases
Immunotherapy
Immunity
Up-Regulation
Viruses

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chiu, Y. L., Shan, L., Huang, H., Haupt, C., Bessell, C., Canaday, D. H., ... Schneck, J. P. (2014). Sprouty-2 regulates HIV-specific T cell polyfunctionality. Journal of Clinical Investigation, 124(1), 198-208. https://doi.org/10.1172/JCI70510

Sprouty-2 regulates HIV-specific T cell polyfunctionality. / Chiu, Yen Ling; Shan, Liang; Huang, Hailiang; Haupt, Carl; Bessell, Catherine; Canaday, David H.; Zhang, Hao; Ho, Ya Chi; Powell, Jonathan; Oelke, Mathias; Margolick, Joseph Bernard; Blankson, Joel N; Griffin, Diane; Schneck, Jonathan P.

In: Journal of Clinical Investigation, Vol. 124, No. 1, 02.01.2014, p. 198-208.

Research output: Contribution to journalArticle

Chiu YL, Shan L, Huang H, Haupt C, Bessell C, Canaday DH et al. Sprouty-2 regulates HIV-specific T cell polyfunctionality. Journal of Clinical Investigation. 2014 Jan 2;124(1):198-208. https://doi.org/10.1172/JCI70510
Chiu, Yen Ling ; Shan, Liang ; Huang, Hailiang ; Haupt, Carl ; Bessell, Catherine ; Canaday, David H. ; Zhang, Hao ; Ho, Ya Chi ; Powell, Jonathan ; Oelke, Mathias ; Margolick, Joseph Bernard ; Blankson, Joel N ; Griffin, Diane ; Schneck, Jonathan P. / Sprouty-2 regulates HIV-specific T cell polyfunctionality. In: Journal of Clinical Investigation. 2014 ; Vol. 124, No. 1. pp. 198-208.
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