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2V
2 T Cells in Macaques1
* Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois, College of Medicine, Chicago, IL 60612;
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China;
Biological Resources Laboratory, University of Illinois, Chicago, IL 60612; and
Institut für Klinische Chemie und Pathobiochemie, Justus-Liebig-Universität Giessen, Giessen, Germany
Although phosphoantigen-specific V
2V
2 T cells appear to play a role in antimicrobial and anticancer immunity, mucosal immune responses and effector functions of these 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 V2V2 T cells that expressed CD8 and produced cytotoxic perforin during their peak expansion. Interestingly, HMBPP-activated V2V2 T cells underwent an extraordinary pulmonary accumulation, which lasted for 3–4 mo, although circulating V2V2 T cells had returned to baseline levels weeks prior. The V2V2 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- up to 15 wk after treatment. Furthermore, the capacity of massively expanded V2V2 T cells to produce cytokines in vivo coincided with an increase in numbers of CD4+ and CD8+ 
β T cells after HMBPP/IL-2 cotreatment as well as substantial perforin expression by CD3+V2– T cells. Thus, the prolonged HMBPP-driven antimicrobial and cytotoxic responses of pulmonary and systemic V2V2 T cells may confer immunotherapeutics against infectious diseases and cancers.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health R01 Grants HL64560 and RR13601 (both to Z.W.C.) and Deutsche Forschungsgemeinschaft Grant JO565/1-1 (to H. J.).
2 Address correspondence and reprint requests to Dr. Zheng W. Chen, 835 South Wolcott Avenue, MC790, Chicago, IL 60612. E-mail address: zchen{at}uic.edu
3 Abbreviations used in this paper: HMBPP, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate; BAL, bronchoalveolar lavage; IPP, isopentenyl pyrophosphate.
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