Transient T Cell Receptor β‐Chain Variable Region–Specific Expansions of CD4+and CD8+T Cells during the Early Phase of Pediatric Human Immunodeficiency Virus Infection: Characterization of Expanded Cell Populations by T Cell Receptor Phenotyping

Abstract

T cell receptor (TCR) repertoire perturbations are commonly detected in CD8⁺ T cells during adult primary human immunodeficiency virus (HIV) infection and have been associated with HIV-specific cytotoxic T cell responses. By use of flow cytometry, transient high-level TCR β-chain variable region-specific expansions of CD4⁺ and CD8⁺ T cells were observed more frequently in HIV-infected children than in children exposed to HIV who remained uninfected. TCR β-chain diversity analysis and diversity-specific polymerase chain reaction were used to study the clonality of expanded CD4⁺ and CD8⁺ subsets. In CD8⁺ T cells, structural features of the complement-determining regions 3 were altered during the course of the expansion, and persistent TCR clonotypes were observed, consistent with antigen-driven selection. In contrast, TCR β-chain variable region-specific expansions without clonotypic overrepresentation or persistence were observed in CD4⁺ T cells, possibly related to HIV-specific helper T cell responses or to the progressive destruction of the CD4⁺ cell compartment.