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Published on: May 7, 2012
Clonal CD8+ T cell expansions in peripheral blood from human immunodeficiency virus type 1-infected children
Elizabeth J McFarland1, Paul A Harding, Christopher C Striebich
1Division of Pediatric Infectious Diseases, University of Colorado Health Sciences Center, Denver 80262, USA. betsy.mcfarland@uchsc.edu
Insights
HIV-1 infection in children often leads to expanded CD8(+) T cell subsets with specific T cell receptor (TCR) beta-chain variable regions. This suggests a limited CD8(+) TCR repertoire diversity during chronic HIV-1 infection.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Human immunodeficiency virus (HIV) type 1 infection impacts the immune system, particularly T cells.
- Understanding T cell receptor (TCR) repertoire dynamics is crucial for assessing immune responses in HIV-1 infection.
Purpose of the Study:
- To quantitatively and qualitatively assess the TCR repertoire in children with HIV-1 infection.
- To investigate the characteristics and specificity of expanded T cell populations in pediatric HIV-1.
Main Methods:
- Flow cytometry and sequencing of the TCR complementarity-determining region 3 (CDR3).
- Analysis of CD8(+) and CD4(+) T cell subsets and their TCR beta-chain variable regions.
- Assessment of T cell functional differentiation markers (e.g., CD28).
Main Results:
- Expanded CD8(+) T cell subsets expressing specific TCR beta-chain variable regions were significantly more common in HIV-1-infected children (75%) than controls (13.5%).
- Oligoclonal populations dominated expanded subsets, with high clone counts, and were associated with older age and lower CD4(+) counts.
- Evidence of functional differentiation to CD28(-) effector cytotoxic T lymphocytes was observed, with HIV-1 specificity noted for expanded clones.
Conclusions:
- HIV-1 infection in children is associated with a contracted and oligoclonal CD8(+) T cell receptor repertoire.
- The findings suggest limited CD8(+) TCR repertoire diversity in the context of chronic HIV-1 infection.
- Functional T cell differentiation occurs within these expanded populations, indicating an active immune response to HIV-1.
Abstract:
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.
