The role of γ δ T cells in generating antiviral factors and β-chemokines in protection against mucosal simian immunodeficiency virus infection
✍ Scribed by Thomas Lehner; Elaine Mitchell; Lesley Bergmeier; Mahavir Singh; Ralf Spallek; Martin Cranage; Graham Hall; Michael Dennis; Francois Villinger; Yufei Wang
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 138 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
In view of the role of + ˇ+ T cells in mucosal protection against infection, the proportion of + Ť 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 + ˇT cells eluted from the rectal mucosa (p X 0.01) and the related iliac lymph nodes (p X 0.0001) in protected as compared with infected macaques. Preferential homing of PKH-26-labeled + ˇ+ T cells from the primed iliac lymph nodes to the rectal and cervico-vaginal mucosa was demonstrated after targeted iliac lymph node as compared with i. m. immunization. Investigations of the mechanism of protection revealed that + ˇ+ T cells can generate antiviral factors, RAN-TES, macrophage inflammatory protein (MIP)-1 § and MIP-1 g which can prevent SIV infection by binding to the CCR5 coreceptors. Up-regulation of + ˇ+ 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 + ˇ+ 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 + ˇ+ T cells. These cells generate antiviral factors and the three g -chemokines that prevent binding and transmission of SIV or M-tropic HIV by the CCR5 coreceptor.