BACKGROUND: The relationship of elevated T cell activation to altered T cell differentiation profiles, each defining features of HIV-1 infection, has not been extensively explored. We hypothesized that anti-retroviral suppression of T cell activation levels would lead to alterations in the T cell differentiation of total and HIV-1 specific CD8+ T cell responses among recently HIV-1 infected adults. METHODOLOGY/PRINCIPAL FINDINGS: We performed a longitudinal study simultaneously measuring T cell activation and maturation markers on both total and antigen-specific T cells in recently infected adults: prior to treatment; after the initiation of HAART; and after treatment was halted. Prior to treatment, HIV-1 Gag-specific CD8+ T cells were predominantly of a highly activated, intermediate memory (CD27+CD28-) phenotype, while CMV pp65-specific CD8+ T cells showed a late memory (CD27-CD28-), low activation phenotype. Participants with the highest fraction of late memory (CD27-CD28-) HIV-1-specific CD8+ T cells had higher CD4+ T cell counts (rho = +0.74, p = 0.004). In turn, those with the highest fraction of intermediate memory (CD27+ CD28-) HIV-1 specific CD8+ T cells had high total CD8+ T cell activation (rho = +0.68, p = 0.01), indicating poorer long-term clinical outcomes. The HIV-1 specific T cell differentiation profile was not readily altered by suppression of T cell activation following HAART treatment. CONCLUSIONS/SIGNIFICANCE: A more differentiated, less activated HIV-1 specific CD8+ T cell response may be clinically protective. Anti-retroviral treatment initiated two to four months after infection lowered T cell activation but had no effect on the differentiation profile of the HIV-1-specific response. Intervention during the first month of acute infection may be required to shift the differentiation phenotype of HIV-1 specific responses to a more clinically favorable profile.
BACKGROUND: The relationship of elevated T cell activation to altered T cell differentiation profiles, each defining features of HIV-1 infection, has not been extensively explored. We hypothesized that anti-retroviral suppression of T cell activation levels would lead to alterations in the T cell differentiation of total and HIV-1 specific CD8+ T cell responses among recently HIV-1 infected adults. METHODOLOGY/PRINCIPAL FINDINGS: We performed a longitudinal study simultaneously measuring T cell activation and maturation markers on both total and antigen-specific T cells in recently infected adults: prior to treatment; after the initiation of HAART; and after treatment was halted. Prior to treatment, HIV-1Gag-specific CD8+ T cells were predominantly of a highly activated, intermediate memory (CD27+CD28-) phenotype, while CMV pp65-specific CD8+ T cells showed a late memory (CD27-CD28-), low activation phenotype. Participants with the highest fraction of late memory (CD27-CD28-) HIV-1-specific CD8+ T cells had higher CD4+ T cell counts (rho = +0.74, p = 0.004). In turn, those with the highest fraction of intermediate memory (CD27+ CD28-) HIV-1 specific CD8+ T cells had high total CD8+ T cell activation (rho = +0.68, p = 0.01), indicating poorer long-term clinical outcomes. The HIV-1 specific T cell differentiation profile was not readily altered by suppression of T cell activation following HAART treatment. CONCLUSIONS/SIGNIFICANCE: A more differentiated, less activated HIV-1 specific CD8+ T cell response may be clinically protective. Anti-retroviral treatment initiated two to four months after infection lowered T cell activation but had no effect on the differentiation profile of the HIV-1-specific response. Intervention during the first month of acute infection may be required to shift the differentiation phenotype of HIV-1 specific responses to a more clinically favorable profile.
Authors: Laila E Gamadia; Ester M M van Leeuwen; Ester B M Remmerswaal; Si-La Yong; Sugianto Surachno; Pauline M E Wertheim-van Dillen; Ineke J M Ten Berge; René A W Van Lier Journal: J Immunol Date: 2004-05-15 Impact factor: 5.422
Authors: Guido Silvestri; Donald L Sodora; Richard A Koup; Mirko Paiardini; Shawn P O'Neil; Harold M McClure; Silvija I Staprans; Mark B Feinberg Journal: Immunity Date: 2003-03 Impact factor: 31.745
Authors: Bhupat D Rawal; Azucena Degula; Ludmila Lebedeva; Robert S Janssen; Frederick M Hecht; Haynes W Sheppard; Michael P Busch Journal: J Acquir Immune Defic Syndr Date: 2003-07-01 Impact factor: 3.731
Authors: Michaela Lucas; Ana L Vargas-Cuero; Georg M Lauer; Eleanor Barnes; Christian B Willberg; Nasser Semmo; Bruce D Walker; Rodney Phillips; Paul Klenerman Journal: J Immunol Date: 2004-02-01 Impact factor: 5.422
Authors: Jason D Barbour; Frederick M Hecht; Terri Wrin; Mark R Segal; Clarissa A Ramstead; Teri J Liegler; Michael P Busch; Christos J Petropoulos; Nicholas S Hellmann; James O Kahn; Robert M Grant Journal: J Infect Dis Date: 2004-06-18 Impact factor: 5.226
Authors: Victor Appay; P Rod Dunbar; Margaret Callan; Paul Klenerman; Geraldine M A Gillespie; Laura Papagno; Graham S Ogg; Abigail King; Franziska Lechner; Celsa A Spina; Susan Little; Diane V Havlir; Douglas D Richman; Norbert Gruener; Gerd Pape; Anele Waters; Philippa Easterbrook; Mariolina Salio; Vincenzo Cerundolo; Andrew J McMichael; Sarah L Rowland-Jones Journal: Nat Med Date: 2002-04 Impact factor: 53.440
Authors: Debbie van Baarle; Stefan Kostense; Egbert Hovenkamp; Graham Ogg; Nening Nanlohy; Margaret F C Callan; Nicole H T M Dukers; Andrew J McMichael; Marinus H J van Oers; Frank Miedema Journal: AIDS Date: 2002-10-18 Impact factor: 4.177
Authors: Jorge R Almeida; David A Price; Laura Papagno; Zaïna Aït Arkoub; Delphine Sauce; Ethan Bornstein; Tedi E Asher; Assia Samri; Aurélie Schnuriger; Ioannis Theodorou; Dominique Costagliola; Christine Rouzioux; Henri Agut; Anne-Geneviève Marcelin; Daniel Douek; Brigitte Autran; Victor Appay Journal: J Exp Med Date: 2007-09-24 Impact factor: 14.307
Authors: Timothy Q Crawford; Lishomwa C Ndhlovu; Alice Tan; Alex Carvidi; Frederick M Hecht; Elizabeth Sinclair; Jason D Barbour Journal: J Virol Date: 2011-09-21 Impact factor: 5.103
Authors: Sara Ferrando-Martínez; Ezequiel Ruiz-Mateos; Ana Hernández; Encarnación Gutiérrez; Maria del Mar Rodríguez-Méndez; Antonio Ordoñez; Manuel Leal Journal: Age (Dordr) Date: 2010-08-11
Authors: Devi SenGupta; Ravi Tandon; Raphaella G S Vieira; Lishomwa C Ndhlovu; Rachel Lown-Hecht; Christopher E Ormsby; Liyen Loh; R Brad Jones; Keith E Garrison; Jeffrey N Martin; Vanessa A York; Gerald Spotts; Gustavo Reyes-Terán; Mario A Ostrowski; Frederick M Hecht; Steven G Deeks; Douglas F Nixon Journal: J Virol Date: 2011-04-27 Impact factor: 5.103
Authors: Ravi Tandon; Maria T M Giret; Devi Sengupta; Vanessa A York; Andrew A Wiznia; Michael G Rosenberg; Esper G Kallas; Lishomwa C Ndhlovu; Douglas F Nixon Journal: PLoS One Date: 2012-09-24 Impact factor: 3.240
Authors: E Saba; J-C Grivel; C Vanpouille; B Brichacek; W Fitzgerald; L Margolis; A Lisco Journal: Mucosal Immunol Date: 2010-02-10 Impact factor: 7.313
Authors: Annette Fox; Nguyen Minh Hoa Le; Peter Horby; H Rogier van Doorn; Vu Trung Nguyen; Hong Ha Nguyen; Trung Cap Nguyen; Dinh Phu Vu; Minh Ha Nguyen; Nguyen Thi Ngoc Diep; Vu Thi Ngoc Bich; Huong Tran Thi Kieu Huong; Walter R Taylor; Jeremy Farrar; Heiman Wertheim; Van Kinh Nguyen Journal: PLoS One Date: 2012-02-20 Impact factor: 3.240