title: CD8 apoptosis may be a predictor of T cell number normalization after immune reconstitution in HIV.
abstract: BACKGROUND
  As part of the Houston Vanguard study, a subset of 10 patients randomized to receive IL-2 therapy were compared to 4 patients randomized to not receive IL-2, for markers of T cell activation and death during the first three cycles of IL-2. All patients were treated with combination antiretroviral therapy (ART) and were virally suppressed. The purpose of the study was to examine the role of CD8(+) T cell death in responses to ART and IL-2 therapy.
  
  
  METHODS
  Lymphocytes were examined at Day 0, 5 and 30 days during three cycles of IL-2 therapy. CD25, CD38, HLA-DR expression and annexin (cell death) were examined on CD4 and CD8 subpopulations. Follow up studies examined CD4 levels and CD4:CD8 reconstitution after 6 years using both univariant and multivariate analyses.
  
  
  RESULTS
  Human lymphocytes responded to IL-2 therapy by upregulation of CD25 on CD4(+) T cells, leading to an increase in CD4 cell counts. CD8(+) T cells did not increase CD25 expression, but upregulated activation antigens (CD38 and DR) and had increased death. At baseline, 7 of the 14 patients had high CD8+ T cell apoptosis (mean 17.0% +/- 6.0). We did an exploratory analysis of immune status after six years, and found that baseline CD8+ T cell apoptosis was correlated with CD4 cell count gain beginning two years post enrollment. Patients with low levels of CD8(+) T cell apoptosis at baseline (mean 2.2% +/- 2.1) had significantly higher CD4 cell counts and more normalized CD4:CD8 ratios than patients with high CD8(+) T cell apoptosis (mean CD4 cell counts 1,209 +/- 164 vs 754 +/- 320 cells/mm(3); CD4:CD8 ratios 1.55 vs. 0.70, respectively).
  
  
  CONCLUSIONS
  We postulate that CD8(+) T cell apoptosis may reflect inherent activation status, which continues in some patients even though viral replication is suppressed which influences the ability of CD4(+) T cells to rebound. Levels of CD8(+) T cell apoptosis may therefore be an independent predictor of immune status, which should be shown in a prospective study.
authors.affiliation: Department of Immunology, Baylor College of Medicine, Houston, Texas, USA. dlewis@bcm.edu
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Lewis
authors.forename: Kimber L
authors.initials: KL
authors.lastname: Gross
authors.forename: Martine M
authors.initials: MM
authors.lastname: Diez
authors.forename: Maria L
authors.initials: ML
authors.lastname: Martinez
authors.forename: Helen N
authors.initials: HN
authors.lastname: Lukefahr
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Kozinetz
authors.forename: Roberto C
authors.initials: RC
authors.lastname: Arduino
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D013997:Time Factors
chemical_list: D017304:Annexin A5; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D051997:ADP-ribosyl Cyclase 1