Antigen-specific Vgamma2Vdelta2 T effector cells confer homeostatic protection against pneumonic plaque lesions.
The possibility that Vgamma2Vdelta2 T effector cells can confer protection against pulmonary infectious diseases has not been tested. We have recently demonstrated that single-dose (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) plus IL-2 treatment can induce prolonged accumulation of Vgamma2Vdelta2 T effector cells in lungs. Here, we show that a delayed HMBPP/IL-2 administration after inhalational Yersinia pestis infection induced marked expansion of Vgamma2Vdelta2 T cells but failed to control extracellular plague bacterial replication/infection. Surprisingly, despite the absence of infection control, expansion of Vgamma2Vdelta2 T cells after HMBPP/IL-2 treatment led to the attenuation of inhalation plague lesions in lungs. Consistently, HMBPP-activated Vgamma2Vdelta2 T cells accumulated and localized in pulmonary interstitials surrounding small blood vessels and airway mucosa in the lung tissues with no or mild plague lesions. These infiltrating Vgamma2Vdelta2 T cells produced FGF-7, a homeostatic mediator against tissue damages. In contrast, control macaques treated with glucose plus IL-2 or glucose alone exhibited severe hemorrhages and necrosis in most lung lobes, with no or very few Vgamma2Vdelta2 T cells detectable in lung tissues. The findings are consist with the paradigm that circulating Vgamma2Vdelta2 T cells can traffic to lungs for homeostatic protection against tissue damages in infection.
Huang
Dan
D
Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, IL 60612, USA.
Chen
Crystal Y
CY
Ali
Zahida
Z
Shao
Lingyun
L
Shen
Ling
L
Lockman
Hank A
HA
Barnewall
Roy E
RE
Sabourin
Carol
C
Eestep
James
J
Reichenberg
Armin
A
Hintz
Martin
M
Jomaa
Hassan
H
Wang
Richard
R
Chen
Zheng W
ZW
D000818:Animals; D002465:Cell Movement; D004195:Disease Models, Animal; D051523:Fibroblast Growth Factor 7 / Q000096:biosynthesis; D006706:Homeostasis; D007376:Interleukin-2 / Q000008:administration & dosage*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008251:Macaca; D010755:Organophosphates / Q000008:administration & dosage*; D010930:Plague / Q000276:immunology* / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015010:Yersinia pestis
C467061:4-hydroxy-3-methyl-2-butenyl diphosphate; D007376:Interleukin-2; D010755:Organophosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051523:Fibroblast Growth Factor 7