Journal ArticleDOI
HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors
Stephen A. Migueles,Alisha C. Laborico,W. Lesley Shupert,M. Shirin Sabbaghian,Ronald L. Rabin,Claire W. Hallahan,Debbie van Baarle,Stefan Kostense,Frank Miedema,Mary McLaughlin,Linda A. Ehler,Julia A. Metcalf,Shuying Liu,Mark Connors +13 more
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Results indicated that nonprogressors were differentiated by increased proliferative capacity of HIV-specific CD8+ T cells linked to enhanced effector function, and the relative absence of these functions in progressors may represent a mechanism by which HIV avoids immunological control.Abstract:
It is unclear why immunological control of HIV replication is incomplete in most infected individuals. We examined here the CD8+ T cell response to HIV-infected CD4+ T cells in rare patients with immunological control of HIV. Although high frequencies of HIV-specific CD8+ T cells were present in nonprogressors and progressors, only those of nonprogressors maintained a high proliferative capacity. This proliferation was coupled to increases in perforin expression. These results indicated that nonprogressors were differentiated by increased proliferative capacity of HIV-specific CD8+ T cells linked to enhanced effector function. In addition, the relative absence of these functions in progressors may represent a mechanism by which HIV avoids immunological control.read more
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PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
Cheryl L. Day,Daniel Kaufmann,Photini Kiepiela,Julia A. Brown,Eshia Moodley,Sharon Reddy,Elizabeth W Mackey,Joseph D. Miller,Alasdair Leslie,Chantal DePierres,Zenele Mncube,Jaikumar Duraiswamy,Baogong Zhu,Quentin Eichbaum,Marcus Altfeld,E. John Wherry,Hoosen M. Coovadia,Philip J. R. Goulder,Philip J. R. Goulder,Philip J. R. Goulder,Paul Klenerman,Rafi Ahmed,Gordon J. Freeman,Bruce D. Walker,Bruce D. Walker,Bruce D. Walker +25 more
TL;DR: The data indicate that the immunoregulatory PD-1/PD-L1 pathway is operative during a persistent viral infection in humans, and define a reversible defect in HIV-specific T-cell function.
Journal ArticleDOI
Lineage relationship and protective immunity of memory CD8 T cell subsets.
E. John Wherry,Volker Teichgräber,Todd C. Becker,David Masopust,Susan M. Kaech,Rustom Antia,Ulrich H. von Andrian,Rafi Ahmed +7 more
TL;DR: It is proposed that TCM and TEM do not necessarily represent distinct subsets, but are part of a continuum in a linear naive → effector → TEM → TCM differentiation pathway.
Journal ArticleDOI
HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T-cells
Michael R. Betts,Martha Nason,Sadie M. West,Stephen C. De Rosa,Stephen A. Migueles,Jonathan Abraham,Michael M. Lederman,Jose M. Benito,Paul A. Goepfert,Mark Connors,Mario Roederer,Richard A. Koup +11 more
TL;DR: The quality of the HIV-specific CD8(+) T-cell functional response serves as an immune correlate of HIV disease progression and a potential qualifying factor for evaluation of HIV vaccine efficacy.
Journal ArticleDOI
Upregulation of PD-1 expression on HIV-specific CD8 + T cells leads to reversible immune dysfunction
Lydie Trautmann,Loury Janbazian,Loury Janbazian,Nicolas Chomont,Elias A. Said,Sylvain Gimmig,Benoit Bessette,Mohamed Rachid Boulassel,Eric Delwart,Homero Sepulveda,Robert Balderas,Jean-Pierre Routy,Jean-Pierre Routy,Elias K. Haddad,Elias K. Haddad,Rafick Pierre Sekaly,Rafick Pierre Sekaly +16 more
TL;DR: Blocking PD-1 engagement to its ligand (PD-L1) enhanced the capacity of HIV-specific CD8+ T cells to survive and proliferate and led to an increased production of cytokines and cytotoxic molecules in response to cognate antigen.
Journal ArticleDOI
T-cell quality in memory and protection: implications for vaccine design
TL;DR: 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.
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Current protocols in immunology
TL;DR: Current Protocols in Immunology is a three-volume looseleaf manual that provides comprehensive coverage of immunological methods from classic to the most cutting edge, including antibody detection and preparation, assays for functional activities of mouse and human cells involved in immune responses, and animal models of autoimmune and inflammatory diseases.
Journal ArticleDOI
Effector and memory T-cell differentiation: implications for vaccine development
TL;DR: The signals required for commitment to this programme of development and the factors that might influence its progression are discussed and models of the pathways of effector and memory T-cell differentiation are discussed.
Journal ArticleDOI
Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections.
Victor Appay,P. Rod Dunbar,Margaret F. C. Callan,Paul Klenerman,Geraldine M. Gillespie,Laura Papagno,Graham S. Ogg,Abigail S. King,Franziska Lechner,Celsa A. Spina,Susan J. Little,Diane V. Havlir,Douglas D. Richman,Norbert H. Gruener,Gerd R. Pape,Anele Waters,Philippa Easterbrook,Mariolina Salio,Vincenzo Cerundolo,Andrew J. McMichael,Sarah Rowland-Jones +20 more
TL;DR: There are significant enrichments at different stages of cellular differentiation in the chronic phase of persistent infection according to the viral specificity, which suggests that distinct memory T-cell populations are established in different virus infections.
Journal ArticleDOI
Phenotypic and Functional Separation of Memory and Effector Human CD8+ T Cells
Dörte Hamann,Paul A. Baars,M.H.G. Rep,Berend Hooibrink,Susana R. Kerkhof-Garde,Michèl R. Klein,René A. W. van Lier +6 more
TL;DR: In this article, two discrete primed subpopulations are found within the circulating human CD8+ T cell subset, i.e., CD45RA−CD45R0+ cells and CD27−CD27− cells.
Journal ArticleDOI
HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage.
Mary Carrington,George W. Nelson,Maureen P. Martin,Teri Kissner,David Vlahov,James J. Goedert,Richard A. Kaslow,Susan Buchbinder,Keith Hoots,Stephen J. O'Brien +9 more
TL;DR: The extended survival of 28 to 40 percent of HIV-1-infected Caucasian patients who avoided AIDS for ten or more years can be attributed to their being fully heterozygous at HLA class I loci, to their lacking the AIDS-associated alleles B*35 and Cw*04, or to both.