Lymphocytes in ASCT and HIV Figure 1. Phenotypical maturation pattern of CD4+ lymphocytes in ASCT recipients (ASCT), HIV-infected patients (HIV) and healthy controls (HC). The percentage of na¨ıve CD4+ T cells (CD45RA+CCR7+) (A), central memory (CD45RA2CCR7+) (B), effector memory (CD45RA2CCR72) (C) and effector cells (CD45RA+CCR72) (D) were compared in the groups. ASCT recipients and HIV-infected patients displayed low percentages of na¨ıve and central memory CD4+ T cells. A relative expansion of effector memory cells was observed in both population. Each central bar represents the median value and each box corresponds to the 25th through 75th percentile (interquartile) range. doi:10.1371/journal.pone.0003616.g001 HC 33.1%, p,0.05 for ASCT versus HC, p.0.05 for HIV versus ASCT and HC). Similarly to what observed in HIV-infected patients, ASCT recipients present a phenotypic CD4+ pattern characterized by a relative expansion of effector memory cells and a loss of central memory cells, which has been hypothesized disadvantageous in chronic infections. CD8+ maturation patterns are preserved in ASCT recipients compared to HIV-infected patients A wholly different scenario was evidenced when CD8+ T cell maturation patterns were analyzed in ASCT recipients and in HIV-infected subjects (Fig. 2). Indeed, while ASCT recipients displayed levels of CD45RA+CCR7+ CD8+ T-cells comparable with healthy controls (ASCT 28.83%; HIV 26.9%; p.0.05), significant reduced levels of na¨ıve CD8 T cells were seen in HIV+ patients (6.07%, p,0.05 for HIV versus HC). Moreover, while CD45RA2CCR72 CD8+ T cells predominated in HIV positive patients, levels of these pre-terminally differentiated cells were significantly lower in ASCT recipients and in healthy controls (ASCT 36.4%, HIV 62.6%, HC 32.3%, p,0.05 for HIV versus ASCT and HC). Higher levels of CD45RA+CCR72 effector CD8+ cells were present in ASCT recipients than in HIV-infected subjects (ASCT 21.07%, HIV 12.55%, p = 0.05), who displayed significantly lower levels of terminal differentiated CD8+ T cells compared to healthy controls (HC 33.2%, p,0.05 for HIV versus HC). These data demonstrate that, unlike the chronic viral model, in ASCT recipients the rapidly replicating CD8+ T cell compartment follow a phenotypic distribution biased toward a terminally differentiated effector cell phenotype. A low effector memory/terminally differentiated CD8+ ratio characterizes ASCT recipients To characterize the imbalance between T cells with different maturative phenotype, we calculated ratios of various subsets of CD4+ and CD8 lymphocytes across the two groups of patients. Ratios between CD4+ subpopulation, CD45RA2CCR7+/ CD45RA2CCR72, CD45RA2CCR72/CD45RA+CCR72 and CD45RA2CCR72/CD45RA+CCR72 evaluated for ASCT recipients failed to uncover significant differences compared to HIV- infected patients (0.12 versus 0.23, 6.83 versus 10.81, 0.57 versus 2.84 respectively). However, the comparison of ASCT recipients with age-matched healthy controls showed significantly low ratios PLoS ONE | www.plosone.org 3 October 2008 | Volume 3 | Issue 10 | e3616