title: Single-cell level response of HIV-specific and cytomegalovirus-specific CD4 T cells correlate with viral control in chronic HIV-1 subtype A infection.
abstract: OBJECTIVE
  HIV-1 subtype A is the second most prevalent subtype globally and is associated with reduced viral load, higher CD4 absolute counts, and slower disease progression. To study the possible role of T cells associated with better outcome, we examined CD4 and CD8 T-cell responses against HIV-1 and cytomegalovirus (CMV) in Ugandans infected with subtype A HIV-1.
  
  
  METHODS
  T-cell responses were investigated using flow cytometry and novel subtype A variant inclusive peptide (VIP) sets designed for this evaluation. CD4 T-cell responses focused primarily on Gag, whereas CD8 T-cell responses were broadly directed against Gag, gp41, and Nef VIP sets. CD4 T cells primarily responded with interferon (IFN)-γ, whereas CD8 cells were more diverse with degranulation (CD107a), IFN-γ, and macrophage inflammatory protein (MIP)-1β production.
  
  
  RESULTS
  No relationship was observed between CD8 T-cell responses and the HIV-1 load. Similarly, the frequency of CD4 T cells responding to these antigens did not associate with viral control. However, in CD4 T cells responding against Gag or CMV, the IFN-γ intensity, indicative of the production at the single-cell level, was inversely proportional to viral load. No significant relationship was found between T-cell effector/memory phenotype and viral control.
  
  
  CONCLUSIONS
  The per cell production of IFN-γ in CD4 T cells responding to HIV-1 or CMV correlated with viral control in chronic HIV-1 subtype A infection. These data suggest that quantitative aspects at the single-cell level may be more important than the frequency of antigen-specific CD4 T cells in HIV-1 subtype A infection control.
authors.affiliation: U.S. Military HIV Research Program, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. meller@hivresearch.org
authors.forename: Michael A
authors.initials: MA
authors.lastname: Eller
authors.forename: Leigh Anne
authors.initials: LA
authors.lastname: Eller
authors.forename: Silvia
authors.initials: S
authors.lastname: Ratto-Kim
authors.forename: Benson J
authors.initials: BJ
authors.lastname: Ouma
authors.forename: Vicky
authors.initials: V
authors.lastname: Lo
authors.forename: Mark
authors.initials: M
authors.lastname: de Souza
authors.forename: David
authors.initials: D
authors.lastname: Guwatudde
authors.forename: Barbara
authors.initials: B
authors.lastname: Nails
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.forename: Fred
authors.initials: F
authors.lastname: Wabwire-Mangen
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.forename: Mary A
authors.initials: MA
authors.lastname: Marovich
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Currier
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D054407:Chemokine CCL4 / Q000378:metabolism; D002908:Chronic Disease; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D054407:Chemokine CCL4; D015700:HIV Envelope Protein gp41; D054301:gag Gene Products, Human Immunodeficiency Virus; C514787:gp41 protein, Human immunodeficiency virus 1; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D007371:Interferon-gamma