The role of γδ T cells in generating antiviral factors and β-chemokines in protection against mucosal simian immunodeficiency virus infection

Thomas Lehner, Elaine Mitchell, Lesley Bergmeier, Mahavir Singh, Ralf Spallek, Martin Cranage, Graham Hall, Michael Dennis, Francois Villinger, Yufei Wang

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

Abstract

In view of the role of γδ+ T cells in mucosal protection against infection, the proportion of γδ T cells was examined in cells eluted from lymphoid and mucosal tissues of macaques immunized with simian immunodeficiency virus (SIV) gp120 and p27 in alum and challenged with live SIV by the rectal mucosal route. This revealed a significant increase in γδ T cells eluted from the rectal mucosa (p < 0.01) and the related lilac lymph nodes (p < 0.0001) in protected as compared with infected macaques. Preferential homing of PKH-26-labeled γδ+ T cells from the primed lilac lymph nodes to the rectal and cervico-vaginal mucosa was demonstrated after targeted lilac lymph node as compared with i. m. immunization. Investigations of the mechanism of protection revealed that γδ+ T cells can generate antiviral factors, RANTES, macrophage inflammatory protein (MIP)-1α and MIP-1β which can prevent SIV infection by binding to the CCR5 coreceptors. Up-regulation of γδ+ T cells was demonstrated by immunization of macaques with heat shock protein (HSP)70 linked to peptides and with granulocyte-macrophage colony-stimulating factor (GM-CSF). This was confirmed by in vitro studies showing that GM-CSF can up-regulate γδ+ T cells from macaques immunized with HSP-linked peptides but not those from naive animals. We suggest that a novel strategy of immunization with HSP70 linked to antigen may generate both cognate immunity to the antigen and innate immunity by virtue of up-regulation of γδ+ T cells. These cells generate antiviral factors and the three β-chemokines that prevent binding and transmission of SIV or M-tropic HIV by the CCR5 coreceptor.

Original languageEnglish
Pages (from-to)2245-2256
Number of pages12
JournalEuropean Journal of Immunology
Volume30
Issue number8
DOIs
Publication statusPublished - 2000

Keywords

  • Mucosal immunity
  • β-chemokine
  • γδ T cell/

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