HIV-specific CD8+ T cells from HIV+ individuals receiving HAART can be expanded ex vivo to augment systemic and mucosal immunity in vivo
Open Access
- 19 May 2011
- journal article
- clinical trial
- Published by American Society of Hematology in Blood
- Vol. 117 (20), 5391-5402
- https://doi.org/10.1182/blood-2010-11-320226
Abstract
Most HIV+ individuals require lifelong highly active antiretroviral therapy (HAART) to suppress HIV replication, but fail to eliminate the virus in part because of residual replication in gut-associated lymphoid tissues (GALT). Naturally elicited HIV-specific CD8+ T cells generated in the acute and chronic infectious phases exhibit antiviral activity, but decrease in number after HAART. Therapeutic vaccines represent a potential strategy to expand cellular responses, although previous efforts have been largely unsuccessful, conceivably because of a lack of responding HIV-specific central-memory CD8+ T cells (Tcm). To determine whether patients receiving HAART possess CD8+ T cells with Tcm qualities that are amenable to augmentation, HIV-specific CD8+ T-cell clones were derived from HIV-reactive CD28+CD8+ T-cell lines isolated from 7 HIV+ HAART-treated patients, expanded ex vivo, and reinfused into their autologous host. Tracking of the cells in vivo revealed that clones could persist for ≥ 84 days, maintain expression and/or re-express CD28, up-regulate CD62L, secrete IL-2, proliferate on cognate Ag encounter and localize to the rectal mucosa. These results suggest some infused cells exhibited phenotypic and functional characteristics shared with Tcm in vivo, and imply that more effective therapeutic vaccination strategies targeting CD8+ Tcm in patients on HAART might provide hosts with expanded, long-lasting immune responses not only systemically but also in GALT. This study is registered at www.clinicaltrials.gov as NCT00110578.Keywords
This publication has 48 references indexed in Scilit:
- Changes in Function of HIV-Specific T-Cell Responses with Increasing Time from InfectionViral Immunology, 2010
- In situ detection of Gag-specific CD8+cells in the GI tract of SIV infected Rhesus macaquesRetrovirology, 2010
- A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapyVaccine, 2009
- Emergence of Polyfunctional CD8+T Cells after Prolonged Suppression of Human Immunodeficiency Virus Replication by Antiretroviral TherapyJournal of Virology, 2008
- Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primatesJCI Insight, 2008
- Virus-specific CD8+ T cells accumulate near sensory nerve endings in genital skin during subclinical HSV-2 reactivationThe Journal of Experimental Medicine, 2007
- Lack of Mucosal Immune Reconstitution during Prolonged Treatment of Acute and Early HIV-1 InfectionPLoS Medicine, 2006
- Viral Suppression and Immune Restoration in the Gastrointestinal Mucosa of Human Immunodeficiency Virus Type 1-Infected Patients Initiating Therapy during Primary or Chronic InfectionJournal of Virology, 2006
- Lineage relationship and protective immunity of memory CD8 T cell subsetsNature Immunology, 2003
- Two subsets of memory T lymphocytes with distinct homing potentials and effector functionsNature, 1999