Vasoactive intestinal peptide receptor 1 is downregulated during expansion of antigen-specific CD8 T cells following primary and secondary Listeria monocytogenes infections

J Neuroimmunol. 2011 May;234(1-2):40-8. doi: 10.1016/j.jneuroim.2011.02.002. Epub 2011 Mar 10.

Abstract

As regulation of CD8 T cell homeostasis is incompletely understood, we investigated the expression profile of the vasoactive intestinal peptide (VIP) receptors, VPAC1 and VPAC2, on CD8 T cells throughout an in vivo immune response. Herein, we show that adoptively transferred CD8 T cells responding to a Listeria monocytogenes infection significantly downregulated, functionally active VPAC1 protein expression during primary and secondary expansion. VPAC1 mRNA expression was restored during contraction and regained naïve levels in primary, but remained low during secondary, memory generation. VIP co-administration with primary infection suppressed CD8 T cell expansion (≈ 50%). VPAC2 was not detected at any time points throughout primary and secondary infections. Collectively, our data demonstrate that functionally active VPAC1 is dynamically downregulated to render expanding CD8 T cells unresponsive to VIP.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adoptive Transfer / methods
  • Animals
  • Antibodies / pharmacology
  • CD3 Complex / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cyclic AMP / metabolism
  • Down-Regulation / immunology*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Flow Cytometry
  • Listeriosis / immunology
  • Listeriosis / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • RNA, Messenger / metabolism
  • Receptors, Vasoactive Intestinal Polypeptide, Type I / genetics
  • Receptors, Vasoactive Intestinal Polypeptide, Type I / metabolism*
  • Thy-1 Antigens / genetics
  • Time Factors
  • Vasoactive Intestinal Peptide / pharmacology

Substances

  • Antibodies
  • CD3 Complex
  • RNA, Messenger
  • Receptors, Vasoactive Intestinal Polypeptide, Type I
  • Thy-1 Antigens
  • Vasoactive Intestinal Peptide
  • Cyclic AMP