title: Increased numbers of primed activated CD8+CD38+CD45RO+ T cells predict the decline of CD4+ T cells in HIV-1-infected patients.
abstract: OBJECTIVE
  To look for surrogate markers in HIV-1 infection that can predict the decline of CD4+ T cells.
  
  
  METHODS
  Multiparameter flow cytometric analyses of CD8+ lymphocytes were performed. These cells were investigated for their expression of the activation marker CD38+ within the naive (CD45RA+) and primed (CD45RO+) subsets. Serial CD4 counts were plotted for each patient and the straight line that best fitted was obtained using least squares regression. Differences in rate of decline were tested using analysis of variance, after each patient was weighted by the reciprocal of the variance.
  
  
  RESULTS
  Baseline levels of percentages of CD8+CD38+ T lymphocytes predict the CD4 decline in HIV-1-infected patients. Within the CD8+ subset, the primed CD8+CD38+CD45RO+ population was responsible for this prediction. Conversely, the naive CD8+CD38+CD45RA+ population was not predictive. Patients who initially showed a percentage of CD8+CD38+ T lymphocytes above the median (> 25%) had a more marked decline in CD4+ T cells when compared to individuals with percentages of CD8+CD38+ T lymphocytes below the median value (79.3 and 21.2 x 10(6)/l mean CD4 cell decline per year, respectively). Similarly, percentages of CD8+CD38+CD45RO+ T cells above the median value (> 7%) were also associated with a more rapid decline (69.4 and 14.2 x 10(6)/l mean CD4+ cell decline per year). These results were statistically significant after adjustment for the baseline CD4 count and beta 2-microglobulin levels.
  
  
  CONCLUSIONS
  Percentages of activated CD8+ cells expressing CD38+ can predict the rate of decline (slope) of the CD4+ T cells. This resides in the CD45RO+ primed population. An early prediction of the CD4+ slope will allow the clinician to target treatment to those patients that are most likely to benefit.
authors.affiliation: Department of Clinical Immunology, Royal Free Hospital and School of Medicine, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Bofill
authors.forename: A
authors.initials: A
authors.lastname: Mocroft
authors.forename: M
authors.initials: M
authors.lastname: Lipman
authors.forename: E
authors.initials: E
authors.lastname: Medina
authors.forename: N J
authors.initials: NJ
authors.lastname: Borthwick
authors.forename: C A
authors.initials: CA
authors.lastname: Sabin
authors.forename: A
authors.initials: A
authors.lastname: Timms
authors.forename: M
authors.initials: M
authors.lastname: Winter
authors.forename: L
authors.initials: L
authors.lastname: Baptista
authors.forename: M A
authors.initials: MA
authors.lastname: Johnson
authors.forename: C A
authors.initials: CA
authors.lastname: Lee
authors.forename: A N
authors.initials: AN
authors.lastname: Phillips
authors.forename: G
authors.initials: G
authors.lastname: Janossy
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D000943:Antigens, Differentiation / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000097:blood; D011237:Predictive Value of Tests; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D017493:Leukocyte Common Antigens; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1