The Transcriptome of Human Cytotoxic T Cells: Similarities and Disparities Among Allostimulated CD4+ CTL, CD8+ CTL and NK cells


* Corresponding author: Philip F. Halloran,


Transcripts expressed in cytotoxic T lymphocytes (CTL) have mechanistic and diagnostic importance in transplantation. We used microarrays to select CTL-associated transcripts (CATs) expressed in human CD4+ CTL, CD8+ CTL and NK cells, excluding transcripts expressed in B cells, monocytes and kidney. This generated three transcript sets: CD4+-associated, CD8+-associated and NK-associated. Surprisingly, many CATs were expressed in effector memory cells e.g. granzyme B/GZMB, interferon-γ/IFNG. Transcript expression was very similar between CD4+ and CD8+ CTL. There were no transcripts highly selective for CD4+ CTL or CD8+ CTL: for example, cytotoxic molecule transcripts (perforin, granzymes, granulysin) were shared between CD8+ CTL and CD4+ CTL although expression remained higher in CD8+ CTL. Transcripts that differentiated between CD8+ CTL and CD4+ CTL were primarily those shared between CD8+ CTL and NK cells (e.g. NK receptors KLRC1, KLRC3, KLRD1, KLRK1). No transcripts could differentiate CD4+ CTL from CD8+ CTL but NK cell-associated transcripts could differentiate NK cells from CTL. This study serves as a foundation for the interpretation of CATs in rejecting allografts and highlights the extensive sharing of CATs among CD4+ CTL, CD8+ CTL and effector memory T cells.