TITLE

In Vitro Priming Recapitulates In Vivo HIV-1 Specific T Cell Responses, Revealing Rapid Loss of Virus Reactive CD4+ T Cells in Acute HIV-1 Infection

AUTHOR(S)
Sabado, Rachel Lubong; Kavanagh, Daniel G.; Kaufmann, Daniel E.; Fru, Karlhans; Babcock, Ethan; Rosenberg, Eric; Walker, Bruce; Lifson, Jeffrey; Bhardwaj, Nina; Larsson, Marie
PUB. DATE
January 2009
SOURCE
PLoS ONE;2009, Vol. 4 Issue 1, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: The requirements for priming of HIV-specific T cell responses initially seen in infected individuals remain to be defined. Activation of T cell responses in lymph nodes requires cell-cell contact between T cells and DCs, which can give concurrent activation of T cells and HIV transmission. Methodology: The study aim was to establish whether DCs pulsed with HIV-1 could prime HIV-specific T cell responses and to characterize these responses. Both infectious and aldrithiol-2 inactivated noninfectious HIV-1 were compared to establish efficiencies in priming and the type of responses elicited. Findings: Our findings show that both infectious and inactivated HIV-1 pulsed DCs can prime HIV-specific responses from naïve T cells. Responses included several CD4+ and CD8+ T cell epitopes shown to be recognized in vivo by acutely and chronically infected individuals and some CD4+ T cell epitopes not identified previously. Follow up studies of acute and recent HIV infected samples revealed that these latter epitopes are among the earliest recognized in vivo, but the responses are lost rapidly, presumably through activation-induced general CD4+ T cell depletion which renders the newly activated HIV-specific CD4+ T cells prime targets for elimination. Conclusion: Our studies highlight the ability of DCs to efficiently prime naïve T cells and induce a broad repertoire of HIV-specific responses and also provide valuable insights to the pathogenesis of HIV-1 infection in vivo.
ACCESSION #
48217690

 

Related Articles

  • HIV'pump'kills with ruthless efficiency.  // New Scientist;9/12/2015, Vol. 227 Issue 3038, p16 

    The article focuses on research into HIV virus transmission using new tissue culture methods which suggests CD4 T-cells are killed by cell-to-cell transmission when the cells are briefly connected and suggests this transmission could explain why HIV vaccines have proven ineffective.

  • Cellular Superspreaders: An Epidemiological Perspective on HIV Infection inside the Body. Talbert-Slagle, Kristina; Atkins, Katherine E.; Yan, Koon-Kiu; Khurana, Ekta; Gerstein, Mark; Bradley, Elizabeth H.; Berg, David; Galvani, Alison P.; Townsend, Jeffrey P. // PLoS Pathogens;May2014, Vol. 10 Issue 5, p1 

    The authors describe evidence from molecular biology and virology suggesting that CD4+ T cell heterogeneity could yield variation in the capability of individual cells to become infected and transmit HIV to other cells. They suggest that the CD4+ T cells heterogeneity in the genital mucosa could...

  • Virus-Specific Regulatory T Cells Ameliorate Encephalitis by Repressing Effector T Cell Functions from Priming to Effector Stages. Zhao, Jingxian; Zhao, Jincun; Perlman, Stanley // PLoS Pathogens;Aug2014, Vol. 10 Issue 8, p1 

    Several studies have demonstrated the presence of pathogen-specific Foxp3+ CD4 regulatory T cells (Treg) in infected animals, but little is known about where and how these cells affect the effector T cell responses and whether they are more suppressive than bulk Treg populations. We recently...

  • Implication of cell-in-cell structures in the transmission of HIV to epithelial cells. Ni, Chao; Huang, Lei; Chen, Yuhui; He, Meifang; Hu, Yazhuo; Liu, Siyang; Fang, Xiangdong; Li, Jingyun; Sun, Qiang; Wang, Xiaoning // Cell Research;Nov2015, Vol. 25 Issue 11, p1265 

    A study which investigated whether the formation of heterotypic cell-in-cell structures could lead to the transmission of HIV from internalized CD4+ T cells to the non-susceptible epithelial cells (ECs) is presented. Topics covered include the existence of heterotypic cell-in-cell structures,...

  • Aggregate complexes of HIV-1 induced by multimeric antibodies. Stieh, Daniel J.; King, Deborah F.; Klein, Katja; Pinghuang Liu; Xiaoying Shen; Hwang, Kwan Ki; Ferrari, Guido; Montefiori, David C.; Haynes, Barton; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Michael, Nelson L.; Robb, Merlin L.; Kim, Jerome H.; Denny, Thomas N.; Tomaras, Georgia D.; Shattock, Robin J. // Retrovirology;2014, Vol. 11 Issue 1, p2 

    Background Antibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible mucosal CD4 T cells and dendritic cells....

  • High Transmitter CD4+ T-Cell Count Shortly after the Time of Transmission in a Study of African Serodiscordant Couples. Karita, Etienne; Price, Matt A; Lakhi, Shabir; Kilembe, William; Kamali, Anatoli; Ruzagira, Eugene; Hunter, Eric; Farmer, Paul; Allen, Susan; Stevens, Gwynn; Chetty, Paramesh; Welsh, Sabrina; Yang, Annie; Gilmour, Jill; Fast, Pat; null, null // PLoS ONE;8/20/2015, Vol. 10 Issue 8, p1 

    Background: 2013 WHO guidelines recommend starting ART at CD4+ T-cell counts ≤500 cells/μL. We present the T-cell counts from adult Africans with HIV shortly following transmission to their sexual partners. Methods: HIV-discordant couples in Zambia, Uganda and Rwanda were followed...

  • Schistosoma haematobium Infection and CD4+ T-Cell Levels: A Cross-Sectional Study of Young South African Women. Kleppa, Elisabeth; Klinge, Kari F.; Galaphaththi-Arachchige, Hashini Nilushika; Holmen, Sigve D.; Lillebø, Kristine; Onsrud, Mathias; Gundersen, Svein Gunnar; Taylor, Myra; Ndhlovu, Patricia; Kjetland, Eyrun F. // PLoS ONE;Mar2015, Vol. 10 Issue 3, p1 

    Schistosoma (S.) haematobium causes urogenital schistosomiasis and has been hypothesized to adversely impact HIV transmission and progression. On the other hand it has been hypothesized that HIV could influence the manifestations of schistosomiasis. In this cross-sectional study, we explored the...

  • Phenotype variation in human immunodeficiency virus type 1 transmission and disease progression. Cavarelli, Mariangela; Scarlatti, Gabriella // Disease Markers;2009, Vol. 27 Issue 3/4, p121 

    Human immunodeficiency virus type I (HIV-1) infects target cells through interaction with the CD4 molecule and chemokine receptors, mainly CCR5 and CXCR4. Viral isolates can be phenotypically classified based on the co-receptor they utilize to infect target cells. Thus, R5 and X4 virus use...

  • Predictors of disease progression in HIV infection: a review. Langford, Simone E; Ananworanich, Jintanat; Cooper, David A // AIDS Research & Therapy;2007, Vol. 4, p11 

    During the extended clinically latent period associated with Human Immunodeficiency Virus (HIV) infection the virus itself is far from latent. This phase of infection generally comes to an end with the development of symptomatic illness. Understanding the factors affecting disease progression...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics