Giuseppe
Emeritus
Dynamic regulation of functionally distinct virus-specific T cells (Proc Natl Acad Sci USA, abstract, edited)
Dynamic regulation of functionally distinct virus-specific T cells
1. Zaza M. Ndhlovu a, 2. Mathias Oelke b, 3. Jonathan P. Schneck b,1, and 4. Diane E. Griffin a,1,2
Author Affiliations
1. aW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; and
2. bDepartments of Pathology and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21218 1.
Contributed by Diane E. Griffin, January 11, 2009 (sent for review November 8, 2009)
2. ↵ 1J.P.S. and D.E.G. contributed equally to this work.
Abstract
The functional capacities of CD8+ T cells important for virus clearance are influenced by interactions with antigen presenting cells (APCs) and CD4+ T cells during initial selection, subsequent expansion, and development of memory. Recently, investigators have shown that polyfunctional T cells correlate best with long-term protection, however, it is still unknown how to stimulate T cells to achieve these responses. To study this, we examined the phenotypes and functions of CD8+ T cells specific for two different virus antigens stimulated ex vivo using either autologous monocyte-derived dendritic cells (moDCs) or HLA-A2-Ig-based artificial APCs (aAPCs). Although similar numbers of influenza virus and measles virus tetramer-positive cells were generated by stimulation with peptide-loaded moDCs and aAPCs, T cell function, assessed by expression of IL-2, IFN-γ, TNF-α, MIP1β, and CD107a, showed that aAPC-generated CD8+ T cells were multifunctional, whereas moDC-generated cells were mostly monofunctional. aAPC-generated cells also produced more of each cytokine per cell than CD8+ T cells generated with moDCs. These phenotypes were not fixed, as changing the culture conditions of expanding T cells from aAPCs to moDCs, and moDCs to aAPCs, reversed the phenotypes. We conclude that CD8+ T cells are heterogeneous in their functionality and that this is dependent, in a dynamic way, on the stimulating APC. These studies will lead to understanding the factors that influence induction of optimal CD8+ T cell function.
* antigen presenting cells
* CD8 T cells
* viral immunity
* multifunctional T cells
Footnotes
* 2To whom correspondence should be addressed. E-mail: dgriffin@jhsph.edu.
* Author contributions:
Z.M.N., J.P.S., and D.E.G. designed research; Z.M.N. and M.O. performed research; M.O. contributed new reagents/analytic tools; Z.M.N. analyzed data; and Z.M.N., M.O., J.S., and D.E.G. wrote the paper.
* The authors declare no conflict of interest.
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<cite cite="http://www.pnas.org/content/107/8/3669.short?rss=1">Dynamic regulation of functionally distinct virus-specific T cells ? PNAS</cite>1. Zaza M. Ndhlovu a, 2. Mathias Oelke b, 3. Jonathan P. Schneck b,1, and 4. Diane E. Griffin a,1,2
Author Affiliations
1. aW. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; and
2. bDepartments of Pathology and Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21218 1.
Contributed by Diane E. Griffin, January 11, 2009 (sent for review November 8, 2009)
2. ↵ 1J.P.S. and D.E.G. contributed equally to this work.
Abstract
The functional capacities of CD8+ T cells important for virus clearance are influenced by interactions with antigen presenting cells (APCs) and CD4+ T cells during initial selection, subsequent expansion, and development of memory. Recently, investigators have shown that polyfunctional T cells correlate best with long-term protection, however, it is still unknown how to stimulate T cells to achieve these responses. To study this, we examined the phenotypes and functions of CD8+ T cells specific for two different virus antigens stimulated ex vivo using either autologous monocyte-derived dendritic cells (moDCs) or HLA-A2-Ig-based artificial APCs (aAPCs). Although similar numbers of influenza virus and measles virus tetramer-positive cells were generated by stimulation with peptide-loaded moDCs and aAPCs, T cell function, assessed by expression of IL-2, IFN-γ, TNF-α, MIP1β, and CD107a, showed that aAPC-generated CD8+ T cells were multifunctional, whereas moDC-generated cells were mostly monofunctional. aAPC-generated cells also produced more of each cytokine per cell than CD8+ T cells generated with moDCs. These phenotypes were not fixed, as changing the culture conditions of expanding T cells from aAPCs to moDCs, and moDCs to aAPCs, reversed the phenotypes. We conclude that CD8+ T cells are heterogeneous in their functionality and that this is dependent, in a dynamic way, on the stimulating APC. These studies will lead to understanding the factors that influence induction of optimal CD8+ T cell function.
* antigen presenting cells
* CD8 T cells
* viral immunity
* multifunctional T cells
Footnotes
* 2To whom correspondence should be addressed. E-mail: dgriffin@jhsph.edu.
* Author contributions:
Z.M.N., J.P.S., and D.E.G. designed research; Z.M.N. and M.O. performed research; M.O. contributed new reagents/analytic tools; Z.M.N. analyzed data; and Z.M.N., M.O., J.S., and D.E.G. wrote the paper.
* The authors declare no conflict of interest.
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