The T cell receptor repertoire of CD8+CD28− T lymphocytes is dominated by expanded clones that persist over time

Abstract

SUMMARY The costimulatory molecule CD28 is expressed on almost all CD4+ T cells, but on only a portion of CD8+ T cells in healthy human adults. αβ T cells may thus be divided into three phenotypically and functionally different subsets: CD4+, CD8+CD28+ and CD8+CD28−. Using peripheral blood lymphocytes from six healthy adults, we have studied the T cell receptor (TCR) repertoire within these subsets by analysis of the distribution of lengths of the complementarity determining region 3 (CDR3) of the beta variable (BV) transcripts and flow cytometric analysis of TCR Vβ usage. Expanded CDR3 lengths were identified in 86% of BV families within CD8+CD28− T cells, but in only 4% within CD4+ T cells, and 35% within CD8+CD28+ T cells (P < 0.01). When sequenced, the majority of expanded peaks were found to be dominated by single clones. Identical expanded clones were found within both CD8+CD28+ and CD8+CD28− subsets, consistent with the belief that CD8+CD28− T cells descend directly from CD8+CD28+ T cells. Greatly expanded CD28− clones were found within both CD8+ and CD4+ subsets and persisted at the same magnitude for up to 4.5 years of observation. The finding of a small proportion of cells expressing Ki-67 showed that some of these clonally expanded cells were in the active stages of the cell cycle, but few of the cells expressed activation markers CD69, CD25, CD71 or CD122. One likely explanation for the persistence of expanded peripheral lymphocyte populations in healthy individuals is the presence of persistent antigen.