title: High CD8+ T cell activation marks a less differentiated HIV-1 specific CD8+ T cell response that is not altered by suppression of viral replication.
abstract: 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.
  
  
  RESULTS
  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
  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.affiliation: Department of Medicine, HIV/AIDS Division, San Francisco General Hospital, University of California San Francisco, San Francisco, California, United States of America. jbarbour@php.ucsf.edu
authors.forename: Jason D
authors.initials: JD
authors.lastname: Barbour
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.forename: Qi
authors.initials: Q
authors.lastname: Xuan Tan
authors.forename: Terence
authors.initials: T
authors.lastname: Ho
authors.forename: Lorrie
authors.initials: L
authors.lastname: Epling
authors.forename: Barry M
authors.initials: BM
authors.lastname: Bredt
authors.forename: Jay A
authors.initials: JA
authors.lastname: Levy
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sinclair
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D015658:HIV Infections / Q000276:immunology / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D010641:Phenotype; D014779:Virus Replication