Depletion of naive CD4 T cells by CXCR4-using HIV-1 variants occurs mainly through increased T-cell death and activation
MD Hazenberg, SA Otto, D Hamann, MTL Roos… - Aids, 2003 - journals.lww.com
MD Hazenberg, SA Otto, D Hamann, MTL Roos, H Schuitemaker, RJ de Boer, F Miedema
Aids, 2003•journals.lww.comObjective: 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 …
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 …
Abstract
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.
Lippincott Williams & Wilkins