TCR T cells in vivo

Whereas most peripheral CD8 T cells highly express CD8 heterodimer in healthy individuals, there is an increase of CD8 low or CD8 T cells in HIV infection or Wiskott-Aldrich syndrome and after bone marrow transplantation. The significance of these uncommon cell populations is not well understood. There has been some question as to whether these subsets and CD8 high cells belong to different ontogenic lineages or whether a fraction of CD8 high cells have down-regulated CD8 chain. Here we assessed clonality of CD8 and CD8 low T cells as well as their phenotypic and functional characteristics. Deduced from surface antigens, cytotoxic granule constituents, and cytokine production, CD8 low cells are exclusively composed of effector memory cells. CD8 cells comprise effector memory cells and terminally differentiated CD45RO CCR7 memory cells. T-cell receptor (TCR) V complementarity-determining region 3 (CDR3) spectratyping analysis and subsequent sequencing of CDR3 cDNA clones revealed polyclonality of CD8 high cells and oligoclonality of CD8 low and CD8 cells. Importantly, some expanded clones within CD8 cells were also identified within CD8 high and CD8 low subpopulations. Furthermore, signal-joint TCR rearrangement excision circles concentration was reduced with the loss of CD8 expression. These results indicated that some specific CD8 high T cells expand clonally, differentiate, and simultaneously down-regulate CD8 chain possibly by an antigen-driven mechanism. Provided that antigenic stimulation directly influences the emergence of CD8 T cells, these cells, which have been previously regarded as of extrathymic origin, may present new insights into the mechanisms of autoimmune diseases and immunodeficiencies, and also serve as a useful biomarker to evaluate the disease activities. (Blood. 2002;100:4090-4097)