Clonal CD8+ T Cell Expansions in Peripheral Blood from Human Immunodeficiency Virus Type 1–Infected Children

• Published in: The Journal of infectious diseases Vol. 186; no. 4; pp. 477 - 485
• Main Authors: McFarland, Elizabeth J., Harding, Paul A., Striebich, Christopher C., MaWhinney, Samantha, Kuritzkes, Daniel R., Kotzin, Brian L.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.08.2002; University of Chicago Press
• Subjects: Adolescent; Amino Acid Sequence; Biological and medical sciences; Blood; CD8-Positive T-Lymphocytes - immunology; Cell lines; Child; Child, Preschool; Clone Cells; Complementarity Determining Regions - chemistry; Complementarity Determining Regions - genetics; Complementarity Determining Regions - metabolism; Cytotoxicity, Immunologic; Female; Flow Cytometry; Genes, T-Cell Receptor beta - genetics; HIV; HIV 1; HIV Infections - immunology; HIV-1 - immunology; Human viral diseases; Humans; Infant; Infections; Infectious diseases; Leukocytes, Mononuclear - immunology; Lymphocyte Activation - immunology; Major Articles; Male; Medical sciences; Molecular Sequence Data; Percentages; Receptors, Antigen, T-Cell, alpha-beta - chemistry; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - metabolism; RNA; Sequence analysis; Sequence Analysis, DNA; T cell antigen receptors; T lymphocytes; T-Lymphocyte Subsets - immunology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Human; Immunopathology; Clonality; T cell receptor; Immune response; HIV-1 virus; Retroviridae; AIDS; Cellular immunity; Immune deficiency; Lentivirus; Cell subpopulation; Infection; Virus; Viral disease; T-Lymphocyte; Immunologic repertoire; Human immunodeficiency virus; Child
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/341939

The T cell receptor (TCR) repertoires of 24 human immunodeficiency virus (HIV) type 1–infected children were determined by flow cytometry in combination with sequencing of the highly variable TCR complementarity-determining region 3, permitting a quantitative and qualitative assessment of TCR repertoire. Expanded subsets of CD8+ cells expressing a particular TCR β-chain variable region were more commonly identified in HIV-1–infected children than in healthy control subjects (75% vs. 13.5%; P<.0001). Older age and lower percentage of CD4+ cells were correlated with expansions. Oligoclonal populations occupied 71%–95% of each expanded subset, and predominant clones had high absolute counts. There was evidence of functional differentiation to CD28− effector cytotoxic T lymphocytes, and cells bearing identical TCRs were identified in both CD28+ and CD28− cell populations. HIV-1 specificity was observed for expanded clones. Children with expansions were not more likely to have increased numbers of CD8+ T cells, a finding consistent with the possibility that the CD8+ TCR repertoire has limited diversity