Prolonged (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate-driven antimicrobial and cytotoxic responses of pulmonary and systemic Vgamma2Vdelta2 T cells in macaques.
Although phosphoantigen-specific Vgamma2Vdelta2 T cells appear to play a role in antimicrobial and anticancer immunity, mucosal immune responses and effector functions of these gammadelta T cells during infection or phospholigand treatment remain poorly characterized. In this study, we demonstrate that the microbial phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) plus IL-2 treatment of macaques induced a prolonged major expansion of circulating Vgamma2Vdelta2 T cells that expressed CD8 and produced cytotoxic perforin during their peak expansion. Interestingly, HMBPP-activated Vgamma2Vdelta2 T cells underwent an extraordinary pulmonary accumulation, which lasted for 3-4 mo, although circulating Vgamma2Vdelta2 T cells had returned to baseline levels weeks prior. The Vgamma2Vdelta2 T cells that accumulated in the lung following HMBPP/IL-2 cotreatment displayed an effector memory phenotype, as follows: CCR5+CCR7-CD45RA-CD27+ and were able to re-recognize phosphoantigen and produce copious amounts of IFN-gamma up to 15 wk after treatment. Furthermore, the capacity of massively expanded Vgamma2Vdelta2 T cells to produce cytokines in vivo coincided with an increase in numbers of CD4+ and CD8+ alphabeta T cells after HMBPP/IL-2 cotreatment as well as substantial perforin expression by CD3+Vgamma2- T cells. Thus, the prolonged HMBPP-driven antimicrobial and cytotoxic responses of pulmonary and systemic Vgamma2Vdelta2 T cells may confer immunotherapeutics against infectious diseases and cancers.
Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois, College of Medicine, Chicago, IL 60612, USA.
Zahida
Z
Ali
Lingyun
L
Shao
Lisa
L
Halliday
Armin
A
Reichenberg
Martin
M
Hintz
Hassan
H
Jomaa
Zheng W
ZW
Chen
D000818:Animals; D000941:Antigens / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D011756:Diphosphates / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000032:analysis; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D008168:Lung / Q000276:immunology*; D008251:Macaca; D009092:Mucous Membrane / Q000276:immunology; D054353:Perforin / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; D000941:Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D011756:Diphosphates; D007135:Immunoglobulin Variable Region; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054353:Perforin; D007371:Interferon-gamma