Antigen-specific Vγ2Vδ2 T effector cells confer homeostatic protection against pneumonic plaque lesions

The possibility that Vγ2Vδ2 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 Vγ2Vδ2 T effec...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-05, Vol.106 (18), p.7553-7558
Main Authors: Huang, Dan, Chen, Crystal Y, Ali, Zahida, Shao, Lingyun, Shen, Ling, Lockman, Hank A, Barnewall, Roy E, Sabourin, Carol, Eestep, James, Reichenberg, Armin, Hintz, Martin, Jomaa, Hassan, Wang, Richard, Chen, Zheng W
Format: Article
Language:English
Subjects:
Biological Sciences
Blood vessels
Hemorrhage
Infections
Inhalation
Lesions
Lungs
Mucosa
Plague
Pneumonic plague
T lymphocytes
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Summary:The possibility that Vγ2Vδ2 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 Vγ2Vδ2 T effector cells in lungs. Here, we show that a delayed HMBPP/IL-2 administration after inhalational Yersinia pestis infection induced marked expansion of Vγ2Vδ2 T cells but failed to control extracellular plague bacterial replication/infection. Surprisingly, despite the absence of infection control, expansion of Vγ2Vδ2 T cells after HMBPP/IL-2 treatment led to the attenuation of inhalation plague lesions in lungs. Consistently, HMBPP-activated Vγ2Vδ2 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 Vγ2Vδ2 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 Vγ2Vδ2 T cells detectable in lung tissues. The findings are consist with the paradigm that circulating Vγ2Vδ2 T cells can traffic to lungs for homeostatic protection against tissue damages in infection.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0811250106