OBJECTIVE: Using SCID-Hu mice models and in vitro culture systems, it has been shown that syncytium inducing/CXCR4 using (X4) HIV-1 variants affect thymic function through infection and killing of CXCR4 thymocytes. The effect of X4-emergence on naive, memory and effector T-cell subset kinetics in vivo is, however, not known. DESIGN: Prospective cohort study. METHODS: Analysis of changes in naive, memory and effector CD4 and CD8 T-cell numbers and cell division before and after the emergence of X4 variants. RESULTS: Significantly lower numbers of CD4 T cells in patients with X4 variants (n = 18) compared to patients with non-syncytium inducing/CCR5 using variants (n = 74) were due to increased loss of naive and CD27 memory CD4 T cells. In addition, emergence of X4 variants was associated with a small but significant decline in naive CD8 T-cell numbers and increased proportions of dividing CD4 and CD8 naive, memory and effector T cells. CONCLUSION: Loss of naive T cells may suggest thymic dysfunction, however, such an effect would explain only part of the accelerated naive CD4 T-cell decline because of the longevity of naive T cells. Our data suggest that the accelerated naive CD4 T-cell decline induced by X4 variants is caused mainly by increased death and recruitment to the memory compartment of these cells.
OBJECTIVE: Using SCID-Hu mice models and in vitro culture systems, it has been shown that syncytium inducing/CXCR4 using (X4) HIV-1 variants affect thymic function through infection and killing of CXCR4 thymocytes. The effect of X4-emergence on naive, memory and effector T-cell subset kinetics in vivo is, however, not known. DESIGN: Prospective cohort study. METHODS: Analysis of changes in naive, memory and effector CD4 and CD8 T-cell numbers and cell division before and after the emergence of X4 variants. RESULTS: Significantly lower numbers of CD4 T cells in patients with X4 variants (n = 18) compared to patients with non-syncytium inducing/CCR5 using variants (n = 74) were due to increased loss of naive and CD27 memory CD4 T cells. In addition, emergence of X4 variants was associated with a small but significant decline in naive CD8 T-cell numbers and increased proportions of dividing CD4 and CD8 naive, memory and effector T cells. CONCLUSION: Loss of naive T cells may suggest thymic dysfunction, however, such an effect would explain only part of the accelerated naive CD4 T-cell decline because of the longevity of naive T cells. Our data suggest that the accelerated naive CD4 T-cell decline induced by X4 variants is caused mainly by increased death and recruitment to the memory compartment of these cells.
Authors: Julian Schulze Zur Wiesch; Adriana Thomssen; Philip Hartjen; Ilona Tóth; Clara Lehmann; Dirk Meyer-Olson; Kristina Colberg; Sebastian Frerk; Dalia Babikir; Stefan Schmiedel; Olaf Degen; Stefan Mauss; Jürgen Rockstroh; Schlomo Staszewski; Pavel Khaykin; Alexander Strasak; Ansgar W Lohse; Gerd Fätkenheuer; Joachim Hauber; Jan van Lunzen Journal: J Virol Date: 2010-11-03 Impact factor: 5.103
Authors: Sandra A Koesters; Lucy Matu; Peter Kiama; Omu Anzala; Joanne Embree; Francis A Plummer; Joshua Kimani; Keith R Fowke Journal: J Clin Immunol Date: 2004-11 Impact factor: 8.317
Authors: Yoshiaki Nishimura; Tatsuhiko Igarashi; Olivia K Donau; Alicia Buckler-White; Charles Buckler; Bernard A P Lafont; Robert M Goeken; Simoy Goldstein; Vanessa M Hirsch; Malcolm A Martin Journal: Proc Natl Acad Sci U S A Date: 2004-08-05 Impact factor: 11.205
Authors: Yan Zhang; Catherine de Lara; Andrew Worth; Andrea Hegedus; Karoliina Laamanen; Peter Beverley; Derek Macallan Journal: PLoS Pathog Date: 2013-04-18 Impact factor: 6.823