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Clinical and Vaccine Immunology, September 2009, p. 1293-1301, Vol. 16, No. 9
1071-412X/09/$08.00+0     doi:10.1128/CVI.00074-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Antiretroviral Therapy Restores Diversity in the T-Cell Receptor Vβ Repertoire of CD4 T-Cell Subpopulations among Human Immunodeficiency Virus Type 1-Infected Children and Adolescents{triangledown}

Li Yin,1 Zhong Chen Kou,1 Carina Rodriguez,3 Wei Hou,2 Maureen M. Goodenow,1 and John W. Sleasman4*

Departments of Pathology, Immunology and Laboratory Medicine,1 Department of Epidemiology and Health Policy Research, Shands Cancer Center, University of Florida, College of Medicine, Gainesville, Florida,2 Division of Infectious Diseases,3 Division of Allergy, Immunology, and Rheumatology, University of South Florida, College of Medicine, St. Petersburg, Florida4

Received 19 February 2009/ Returned for modification 8 April 2009/ Accepted 2 July 2009

Human immunodeficiency virus (HIV) type 1 infection perturbs the T-cell receptor (TCR) Vβ repertoire. The TCR CDR3 length diversity of individual Vβ families was examined within CD45RA and CD45RO CD4 T cells to assess the impact of the virus on clonality throughout CD4 T-cell activation and differentiation. A cross-sectional and longitudinal cohort study of 13 HIV-infected and 8 age-matched healthy children and adolescents examined the Vβ CDR3 length profiles within CD4 T-cell subsets by the use of spectratyping. HIV-infected subjects demonstrated higher numbers of perturbations in CD4 CD45RA T cells (5.8 ± 4.9 Vβ families) than healthy individuals (1.6 ± 1.8 Vβ families) (P = 0.04). Surprisingly, CD4 CD45RO central memory T cells from infected subjects showed no increased perturbations compared to the perturbations for the same cells from healthy subjects (2.9 ± 3.1 and 1.1 ± 1.8 Vβ families, respectively; P = 0.11). CD4 CD45RA TCR perturbations were higher among infected subjects with >25% CD4 cells than healthy subjects (mean number of perturbed Vβ families, 6.6 ± 5.4; P = 0.04). No correlations between perturbations in CD4 subsets and pretherapy age or viral load were evident. In contrast to CD8 T cells, HIV induces TCR disruptions within CD45RA but not CD45RO CD4 T cells. Therapy-induced viral suppression resulted in increases in thymic output and the normalization of the diversity of TCR within CD45RA CD4 T cells after 2 months of treatment. Perturbations occur prior to CD4 T-cell attrition and normalize with effective antiretroviral therapy. The impact of HIV on the diversity of TCR within naïve, central memory, and effector memory CD4 T cells is distinctly different from that in CD8 T cells.

* Corresponding author. Mailing address: Division of Allergy, Immunology & Rheumatology, Department of Pediatrics, University of South Florida/All Children's Hospital, 801 Sixth Street South (Box 9350), St. Petersburg, FL 33701. Phone: (727) 767-4470. Fax: (727) 767-8542. E-mail: jsleasma{at}health.usf.edu

{triangledown} Published ahead of print on 15 July 2009.

Clinical and Vaccine Immunology, September 2009, p. 1293-1301, Vol. 16, No. 9
1071-412X/09/$08.00+0     doi:10.1128/CVI.00074-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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