Depletion of naive CD4 T cells by CXCR4-using HIV-1 variants occurs mainly through increased T-cell death and activation.
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.


METHODS
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.


CONCLUSIONS
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.
Hazenberg
Mette D
MD
Department of Clinical Viro-Immunology, Sanquin Research at CLB and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands.
Otto
Sigrid A
SA
Hamann
Dörte
D
Roos
Marijke Th L
MT
Schuitemaker
Hanneke
H
de Boer
Rob J
RJ
Miedema
Frank
F
D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016923:Cell Death; D002455:Cell Division; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D019562:Viral Load
D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7