The role of gamma delta T cells in generating antiviral factors and beta-chemokines in protection against mucosal simian immunodeficiency virus infection

In view of the role of gamma delta(+) T cells in mucosal protection against infection, the proportion of is 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 gamma delta T cells eluted from the rectal mucosa (p <0.01) and the related iliac lymph nodes (p <0.0001) in protected as compared with infected macaques. Preferential homing of PKH-26-labeled gamma delta 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 gamma delta(+) T cells can generate antiviral factors, RANTES, macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta which can prevent SIV infection by binding to the CCR5 coreceptors. Up-regulation of gamma delta(+) 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 gamma delta(+) 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 gamma delta(+) T cells. These cells generate antiviral factors and the three beta-chemokines that prevent binding and transmission of SIV or M-tropic HIV by the CCR5 coreceptor.