Diversity of the T-cell receptor BV repertoire in HIV-1-infected patients reflects the biphasic CD4+ T-cell repopulation kinetics during highly active antiretroviral therapy.
OBJECTIVE
Highly active antiretroviral therapy (HAART) induces a decline in viral load and a biphasic increase in peripheral blood CD4+ T-cell counts in HIV-infected patients. To evaluate the effect of HAART on T-cell receptor (TCR) diversity of repopulating naive and memory CD4+ T cells, complementarity determining region 3 (CDR3) spectratyping was performed.


METHODS
For four patients treated with HAART, CD45RO+ (memory) and CD45RA+ (naive) CD4+ T cells were isolated from peripheral blood leukocyte samples obtained 1 week before, 1-2 months after, and 9-11 months after start of treatment.


METHODS
CDR3 regions were amplified by TCR-BV-specific nested PCR from CD4+ T-cell subsets. CDR3 size distributions and single-strand conformation polymorphism profiles were compared as an indication for TCR diversity.


RESULTS
Increasing blood CD4+ T-cell counts during the first 2 months of treatment coincided with increased perturbation of CDR3 patterns in CD4+ T-cell subsets, suggesting an early oligoclonal repopulation. At later timepoints, CDR3 size diversity increased when T-cell counts did not substantially decrease. Memory and naive CD4+ T cells generally showed comparable levels of perturbation.


CONCLUSIONS
Diversity of the TCR repertoire reflected biphasic T-cell repopulation during HAART, compatible with initial redistribution and later CD4+ T-cell production. Sustained elevation of T-cell counts will in principle result in restoration of TCR diversity.
Kostense
S
S
Department of Clinical Viro-Immunology, CLB Sanquin Blood Supply Foundation and Laboratory for Clinical and Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands.
Raaphorst
F M
FM
Notermans
D W
DW
Joling
J
J
Hooibrink
B
B
Pakker
N G
NG
Danner
S A
SA
Teale
J M
JM
Miedema
F
F
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007137:Immunoglobulin alpha-Chains / Q000276:immunology*; D017493:Leukocyte Common Antigens; D018807:Polymorphism, Single-Stranded Conformational; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*
D019380:Anti-HIV Agents; D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D007137:Immunoglobulin alpha-Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens