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.
|Number of pages||12|
|Journal||European Journal of Immunology|
|Publication status||Published - 2000|
- Mucosal immunity
- γδ T cell/