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The Journal of Immunology, 2007, 178: 43.21.
Copyright © 2007 by The American Association of Immunologists, Inc.
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43.21

Mycobacteria Induce Protective Effector Functions in a Subset of Nonprotective Phosphoantigen-reactive {gamma}9{delta}2 T cells

Charles T Spencer1,2, Getahun Abate2, Azra Blazevic2 and Daniel F Hoft1,2

1 Molecular Microbiology and Immunology, 2 Internal Medicine, St. Louis University, 3635 Vista Ave FDT 8N, St. Louis, MO, 63110

Abstract

Human {gamma}9{delta}2 T cells expand and produce protective cytokine and cytolytic responses during mycobacterial infection. {gamma}9{delta}2 T cells are also stimulated by nonpeptidic phosphoantigens (i.e-IPP, HMB-PP), expressed by intracellular mycobacteria and infected cells. Therefore, purified phosphoantigens could be useful components of new vaccines or immunotherapeutics by stimulating protective {gamma}9{delta}2 T cells. However, it is unclear whether {gamma}9{delta}2 T cells induced by phosphoantigens can protect against mycobacterial replication. We show that while BCG-expanded {gamma}9{delta}2 T cells potently inhibit intracellular mycobacterial growth, IPP/HMB-PP-expanded {gamma}9{delta}2 T cells fail to inhibit intracellular mycobacteria, although both lyse Daudi targets. TLR co-stimulation during IPP expansion also failed to induce anti-mycobacterial {gamma}9{delta}2 T cells. TCR spectratyping and CDR3 sequencing demonstrated that BCG-expanded {gamma}9{delta}2 T cells expressed significantly less TCR sequence diversity than IPP-expanded {gamma}9{delta}2 T cells. BCG-expanded {gamma}9{delta}2 T cells respond similarly to BCG- and IPP-stimulation, while IPP-expanded {gamma}9{delta}2 T cells responded poorly to BCG. BCG appears to stimulate an antigen-specific focusing event in {gamma}9{delta}2 T cells while IPP acts like a mitogen with broad {gamma}9{delta}2 T cell reactivity. The antigens and/or co-stimulatory signals required to induce protective {gamma}9{delta}2 T cells remain to be identified.

Support: NIH R01-AI-48391, VTEU NO1-AI-25464





This Article
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