title: Expansion of pre-existing, lymph node-localized CD8+ T cells during supervised treatment interruptions in chronic HIV-1 infection.
abstract: To date, most studies have focused on the characterization of HIV-1-specific cellular immune responses in the peripheral blood (PB) of infected individuals. Much less is known about the comparative magnitude and breadth of responses in the lymphoid tissue. This study analyzed HIV-1-specific CD8+ T cell responses simultaneously in PB and lymph nodes (LNs) of persons with chronic HIV-1 infection and assessed the dynamics of these responses during antiretroviral treatment and supervised treatment interruption (STI). In untreated chronic infection, the magnitude of epitope-specific CD8+ T cell activity was significantly higher in LNs than in PB. Responses decreased in both compartments during highly active antiretroviral therapy, but this decline was more pronounced in PB. During STI, HIV-1-specific CD8+ T cell responses in PB increased significantly. Enhancement in breadth and magnitude was largely due to the expansion of pre-existing responses in the LNs, with new epitopes infrequently targeted. Taken together, these data demonstrate that HIV-1-specific CD8+ T cells are preferentially located in the LNs, with a subset of responses exclusively detectable in this compartment. Furthermore, the enhanced CD8+ T cell responses observed during STI in chronically infected individuals is largely due to expansion of pre-existing virus-specific CD8+ T cells, rather than the induction of novel responses.
authors.affiliation: Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Claus
authors.initials: C
authors.lastname: Schneider
authors.forename: Robert L
authors.initials: RL
authors.lastname: Eldridge
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Feeney
authors.forename: Dirk
authors.initials: D
authors.lastname: Meyer-Olson
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Stellbrink
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002908:Chronic Disease; D002985:Clinical Protocols; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology*; D008297:Male; D013223:Statistics as Topic; D044465:White People
chemical_list: D000939:Epitopes