The role of gammadelta T cells in generating antiviral factors and beta-chemokines in protection against mucosal simian immunodeficiency virus infection.
In view of the role of gammadelta(+) T cells in mucosal protection against infection, the proportion of gamma delta 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 gammadelta 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 gammadelta(+) 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 gammadelta(+) T cells can generate antiviral factors, RANTES, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta which can prevent SIV infection by binding to the CCR5 coreceptors. Up-regulation of gammadelta(+) 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 gammadelta(+) 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 gammadelta(+) 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.
Department of Immunobiology, Guy's, King's and St. Thomas' Hospital Medical School, London, GB. thomas.lehner@kcl.ac.uk
T
T
Lehner
E
E
Mitchell
L
L
Bergmeier
M
M
Singh
R
R
Spallek
M
M
Cranage
G
G
Hall
M
M
Dennis
F
F
Villinger
Y
Y
Wang
D000818:Animals; D019742:Chemokines, CC / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology; D018928:Immunity, Mucosal; D007114:Immunization; D007376:Interleukin-2 / Q000494:pharmacology; D008253:Macaca mulatta; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D019713:Receptors, CCR5 / Q000502:physiology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*; D014765:Viral Vaccines / Q000276:immunology
D019742:Chemokines, CC; D018840:HSP70 Heat-Shock Proteins; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019713:Receptors, CCR5; D014765:Viral Vaccines