Extrathymic CD4/CD8 double positive T cells

Abstract

Mature T lymphocytes expressing the αβ T cell receptor are generally classified as either CD4 + or CD8 +, based on the mutually exclusive expression of these two lymphocyte coreceptors. Contrary to this conventional division, there is considerable evidence that significant numbers of CD4/CD8 double positive (DP) lymphocytes exist in the peripheral blood and secondary lymphoid tissues of swine, chickens and monkeys. Although CD4/CD8 DP T cells are rarely present in human peripheral blood the relative percentage of this lymphocyte population can increase spontaneously in healthy individuals and in persons suffering from certain disease conditions. DP can also be found among those T cells infiltrating arthritic joints, rejected kidney grafts and certain tumors. In humans, and rats, CD4/CD8 DP T cells appear transiently following activation of their progenitors. Murine DP cells have been described as a subset of intraepithelial lymphocytes (IELs). However, the relationship of IELs to DP cells in the peripheral blood of other species is unknown. Because of their unconventional phenotype and rarity in human and mice, most immunologists have ignored extrathymic CD4/CD8 DP lymphocytes. Nevertheless, their abundance in the peripheral blood of swine, monkeys and chickens makes it impossible to dismiss this lymphocyte population. Here are reports that have described extrathymic lymphocytes exhibiting a CD4 +CD8 dim phenotype in several species reviewed. Swine and monkey lymphocytes with this phenotype are represented by small resting cells that simultaneously express CD4 and CD8α molecules. The available evidence favors the notion that such DP T cells in swine are comprised predominantly of MHC class II restricted memory CD4 + helper T cells that after activation have acquired the ability to express the CD8α chain and then to maintain this DP phenotype. Moreover, porcine CD4/CD8 DP T cells appear to be comprised of memory cells due to their ability to respond to recall antigen, resilience to thymectomy, increase in proportion with age, expression of memory T cell markers, production of interferon-γ and localization to inflammatory sites. Some of these characteristics are also descriptive of human and monkey CD4/CD8 DP T cells. Thus, in swine, humans and monkeys, these phenotypically distinct lymphocytes appear to represent a primed T cell subset. The possible functional significance of the simultaneous expression of the CD4 and CD8 co-receptors on mature T cells is discussed.