association of differentiation state of cd4+ t cells and disease progression in hiv-1 perinatally infected children协会cd4 + t细胞的分化状态和疾病进展在hiv - 1位围产期感染孩子.pdf

Association of Differentiation State of CD4+ T Cells and Disease Progression in HIV-1 Perinatally Infected Children 1 1 1 2 2 Elizabeth R. Sharp , Christian B. Willberg , Peter J. Kuebler , Jacob Abadi , Glenn J. Fennelly , Joanna 2 2 2 1 Dobroszycki , Andrew A. Wiznia , Michael G. Rosenberg , Douglas F. Nixon * 1 Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America, 2 Jacobi Medical Center, Bronx, New York, United States of America Abstract Background: In the USA, most HIV-1 infected children are on antiretroviral drug regimens, with many individuals surviving through adolescence and into adulthood. The course of HIV-1 infection in these children is variable, and understudied. Methodology/Principal Findings: We determined whether qualitative differences in immune cell subsets could explain a slower disease course in long term survivors with no evidence of immune suppression (LTS-NS; CD4%$25%) compared to those with severe immune suppression (LTS-SS; CD4%#15%). Subjects in the LTS-NS group had significantly higher ¨ frequencies of naıve (CCR7+CD45RA+) and central memory (CCR7+CD45RA 2) CD4+ T cells compared to LTS-SS subjects (p = 0.0005 and ,0.0001, respectively). Subjects in the rapid progressing group had significantly higher levels of CD4+ TEMRA (CCR72CD45RA+) cells compared to slow progressing subjects (p,0.0001). Conclusions/Significance: Rapid disease progression in vertical infection is associated with significantly higher levels of CD4+ TEMRA (CCR72C