Journal ArticleDOI
T-cell quality in memory and protection: implications for vaccine design
TLDR
The importance of using multiparameter flow cytometry to better understand the functional capacity of effector and memory T-cell responses, thereby enabling the development of preventative and therapeutic vaccine strategies for infections is highlighted.Abstract:
T cells mediate effector functions through a variety of mechanisms. Recently, multiparameter flow cytometry has allowed a simultaneous assessment of the phenotype and multiple effector functions of single T cells; the delineation of T cells into distinct functional populations defines the quality of the response. New evidence suggests that the quality of T-cell responses is crucial for determining the disease outcome to various infections. This Review highlights the importance of using multiparameter flow cytometry to better understand the functional capacity of effector and memory T-cell responses, thereby enabling the development of preventative and therapeutic vaccine strategies for infections.read more
Citations
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Journal ArticleDOI
Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand
Supachai Rerks-Ngarm,Punnee Pitisuttithum,Sorachai Nitayaphan,Jaranit Kaewkungwal,Joseph Chiu,Robert Paris,Nakorn Premsri,Chawetsan Namwat,Mark de Souza,Elizabeth Adams,Michael Benenson,Sanjay Gurunathan,Jim Tartaglia,John G. McNeil,Donald P. Francis,Donald Stablein,Deborah L. Birx,Supamit Chunsuttiwat,Chirasak Khamboonruang,Prasert Thongcharoen,Merlin L. Robb,Nelson L. Michael,Prayura Kunasol,Jerome H. Kim +23 more
TL;DR: This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk and offer insight for future research.
Journal ArticleDOI
mTOR regulates memory CD8 T-cell differentiation
Koichi Araki,Alexandra P. Turner,Virginia O. Shaffer,Shivaprakash Gangappa,Susanne A. Keller,Martin F. Bachmann,Christian P. Larsen,Rafi Ahmed +7 more
TL;DR: It is shown that mTOR (mammalian target of rapamycin, also known as FRAP1) is a major regulator of memory CD8 T-cell differentiation, and in contrast to what was expected, the immunosuppressive drug Rapamycin has immunostimulatory effects on the generation of memoryCD8 T cells.
Journal ArticleDOI
Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells
TL;DR: The differentiation of T cells producing only IL-22 was efficiently induced in naive T cells by plasmacytoid dendritic cells in an IL-6- and tumor necrosis factor–dependent way and delineate a previously unknown subset of human CD4+ effector T cells dedicated to skin pathophysiology.
Journal ArticleDOI
SPICE: exploration and analysis of post-cytometric complex multivariate datasets.
TL;DR: Algorithms and a graphical interface originally developed to support the analysis of T cell functional profiles are reported on and a statistic for the nonparametric comparison of complex distributions to test for difference between groups of samples based on multi‐component measurements is defined.
Journal ArticleDOI
HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case–cohort analysis
M. Juliana McElrath,M. Juliana McElrath,Stephen C. De Rosa,Stephen C. De Rosa,Zoe Moodie,Sheri Dubey,Lisa Kierstead,Holly Janes,Olivier D. Defawe,Donald K. Carter,John Hural,Rama Akondy,Susan Buchbinder,Michael N. Robertson,Devan V. Mehrotra,Steven G. Self,Steven G. Self,Lawrence Corey,Lawrence Corey,John W. Shiver,Danilo R. Casimiro +20 more
TL;DR: Consistent with previous trials, the MRKAd5 HIV-1 gag/pol/nef vaccine was highly immunogenic for inducing HIV-specific CD8+ T cells and suggest that future candidate vaccines have to elicit responses that either exceed in magnitude or differ in breadth or function from those recorded in this trial.
References
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Journal ArticleDOI
Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor.
Nikhil S. Joshi,Weiguo Cui,Anmol Chandele,Heung Kyu Lee,David Urso,James Hagman,Laurent Gapin,Susan M. Kaech +7 more
TL;DR: A mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and regulates their memory cell potential is elucidated.
Journal ArticleDOI
Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation
Michael R. Betts,Jason M. Brenchley,David Price,Stephen C. De Rosa,Daniel C. Douek,Mario Roederer,Richard A. Koup +6 more
TL;DR: A novel technique to enumerate antigen-specific CD8+ T cells using a marker expressed on the cell surface following activation induced degranulation, a necessary precursor of cytolysis, and CD107-expressing CD8+, expressing cognate T cell receptors (TCR), is presented.
Journal ArticleDOI
Viral Persistence Alters CD8 T-Cell Immunodominance and Tissue Distribution and Results in Distinct Stages of Functional Impairment
TL;DR: A model is proposed in which antigen levels drive the hierarchical loss of different CD8 T-cell effector functions during chronic infection, leading to distinct stages of functional impairment and eventually to physical deletion of virus-specific T cells.
Journal ArticleDOI
Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major.
Patricia A. Darrah,Dipti T. Patel,Paula M De Luca,Ross W. B. Lindsay,Dylan F. Davey,Barbara J. Flynn,Søren T. Hoff,Peter Andersen,Steven G. Reed,Sheldon L. Morris,Mario Roederer,Robert A. Seder +11 more
TL;DR: The quality of a CD4+ T-cell cytokine response can be a crucial determinant in whether a vaccine is protective, and may provide a new and useful prospective immune correlate of protection for vaccines based on T-helper type 1 (TH1) cells.
Journal ArticleDOI
Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity.
John W. Shiver,Tong-Ming Fu,Ling Chen,Danilo R. Casimiro,Mary-Ellen Davies,Robert K. Evans,Zhiqiang Zhang,Adam J. Simon,Wendy L. Trigona,Sheri Dubey,Lingyi Huang,Virginia Harris,Romnie Long,Xiaoping Liang,Larry Handt,William A. Schleif,Lan Zhu,Daniel C. Freed,Natasha Persaud,Liming Guan,Kara Punt,Aimin Tang,Minchun Chen,Keith A. Wilson,Kelly B. Collins,Gwendolyn J. Heidecker,V. Rose Fernandez,Helen C. Perry,Joseph G. Joyce,Karen M. Grimm,James C. Cook,Paul M. Keller,Denise S. Kresock,Henryk Mach,Robert D. Troutman,Lynne Isopi,Donna M. Williams,Zheng Xu,Kathryn E. Bohannon,David B. Volkin,David C. Montefiori,Ayako Miura,Georgia R. Krivulka,Michelle A. Lifton,Marcelo J. Kuroda,Jörn E. Schmitz,Norman L. Letvin,Michael J. Caulfield,Andrew J. Bett,Rima Youil,David C. Kaslow,Emilio A. Emini +51 more
TL;DR: The replication-defective adenovirus is a promising vaccine vector for development of an HIV-1 vaccine and elicited by a replication-incompetent Ad5 vector, used either alone or as a booster inoculation after priming with a DNA vector.