Clonal CD8+ T cell expansions in peripheral blood from human immunodeficiency virus type 1-infected children.
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 beta-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.
Division of Pediatric Infectious Diseases, University of Colorado Health Sciences Center, Denver 80262, USA. betsy.mcfarland@uchsc.edu
Elizabeth J
EJ
McFarland
Paul A
PA
Harding
Christopher C
CC
Striebich
Samantha
S
MaWhinney
Daniel R
DR
Kuritzkes
Brian L
BL
Kotzin
D000293:Adolescent; D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D016176:T-Lymphocyte Subsets / Q000276:immunology
D022801:Complementarity Determining Regions; D016693:Receptors, Antigen, T-Cell, alpha-beta