Endogenous matrix metalloproteinases 2 and 9 regulate activation of CD4+and CD8+ T cells

Heather L. Benson, Shahriar Mobashery, Mayland Chang, Farrah Kheradmand, Jeong Soo Hong, Gerald N. Smith, Rebecca A. Shilling, David S. Wilkes

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

We reported that inhibiting matrix metalloproteinases (MMP), known to remodel the extracellular matrix, also down-regulated antigen-specific T-cell responses. However, the direct role of MMP2 and MMP9 in regulating intracellular function in T cells is unknown. Markers of cellular activation and cytokine profiles were examined in anti-CD3-stimulated wild-type C57BL/6 mouse-derived CD4+ or CD8+ T cells, or MMP2- or MMP9-deficient (-/-) mice. MMP-sufficient T cells were also treated with SB-3CT, a highly selective inhibitor of MMP2 and MMP9. The effect of MMP-specific inhibition on T cell-dependent, antigen-specific murine lung injury was examined in vivo. SB-3CT induced dose-dependent reductions in anti-CD3-stimulated T-cell proliferation. Although MMP2-/- cells were reduced 20%, anti-CD3-induced proliferation was down-regulated 80-85% in MMP9-/- or in SB-3CT-treated wild-type CD4+ and CD8+ T cells. Intracellular calcium flux was augmented in response toMMP inhibition or deficiency in the same cells, and IL-2 production was reduced in CD4+ and CD8+ MMP9-/- T cells. SB-3CT-mediated MMP2 and MMP9 inhibition abrogated antigen-specific CD8+ T cell-mediated lung injury in vivo. MMPs, particularly MMP9, may function intracellularly to regulate T-cell activation. T cell-targeted MMP inhibition may provide a novel approach of immune regulation in the treatment of T cell-mediated diseases.

Original languageEnglish
Pages (from-to)700-708
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume44
Issue number5
DOIs
StatePublished - May 1 2011

Fingerprint

T-cells
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Chemical activation
T-Lymphocytes
Matrix Metalloproteinases
Lung Injury
Antigens
CD8 Antigens
Cell proliferation
Inbred C57BL Mouse
Interleukin-2
Extracellular Matrix
Cell Proliferation

Keywords

  • Matrix metalloproteinase 2
  • Matrix metalloproteinase 9
  • SB-3CT
  • T cells

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Benson, H. L., Mobashery, S., Chang, M., Kheradmand, F., Hong, J. S., Smith, G. N., ... Wilkes, D. S. (2011). Endogenous matrix metalloproteinases 2 and 9 regulate activation of CD4+and CD8+ T cells. American Journal of Respiratory Cell and Molecular Biology, 44(5), 700-708. https://doi.org/10.1165/rcmb.2010-0125OC

Endogenous matrix metalloproteinases 2 and 9 regulate activation of CD4+and CD8+ T cells. / Benson, Heather L.; Mobashery, Shahriar; Chang, Mayland; Kheradmand, Farrah; Hong, Jeong Soo; Smith, Gerald N.; Shilling, Rebecca A.; Wilkes, David S.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 44, No. 5, 01.05.2011, p. 700-708.

Research output: Contribution to journalArticle

Benson, HL, Mobashery, S, Chang, M, Kheradmand, F, Hong, JS, Smith, GN, Shilling, RA & Wilkes, DS 2011, 'Endogenous matrix metalloproteinases 2 and 9 regulate activation of CD4+and CD8+ T cells', American Journal of Respiratory Cell and Molecular Biology, vol. 44, no. 5, pp. 700-708. https://doi.org/10.1165/rcmb.2010-0125OC
Benson, Heather L. ; Mobashery, Shahriar ; Chang, Mayland ; Kheradmand, Farrah ; Hong, Jeong Soo ; Smith, Gerald N. ; Shilling, Rebecca A. ; Wilkes, David S. / Endogenous matrix metalloproteinases 2 and 9 regulate activation of CD4+and CD8+ T cells. In: American Journal of Respiratory Cell and Molecular Biology. 2011 ; Vol. 44, No. 5. pp. 700-708.
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