Extrathymic CD4/CD8 double positive T cells

Mature T lymphocytes expressing the ap T cell receptor are generally classi fied as either CD4(+) or CD8(+), based on the mutually exclusive expression of these two lymphocyte coreceptors. Contrary to this conventional divisio n, there is considerable evidence that significant numbers of CD4/CDs doubl e positive (DP) lymphocytes exist in the peripheral blood and secondary lym phoid tissues of swine, chickens and monkeys. Although CD4/CD8 DP T cells a re rarely present in human peripheral blood the relative percentage of this lymphocyte population can increase spontaneously in healthy individuals an d in persons suffering from certain disease conditions. DP can also be foun d among those T cells infiltrating arthritic joints, rejected kidney grafts and certain tumors. In humans, and rats, CD4/CDs DP T cells appear transie ntly following activation of their progenitors. Murine DP cells have been d escribed as a subset of intraepithelial lymphocytes (LELs). However, the re lationship 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. N evertheless, their abundance in the peripheral blood of swine, monkeys and chickens makes it impossible to dismiss this lymphocyte population. Here ar e reports that have described extrathymic lymphocytes exhibiting a CD4(+)CD 8(dim) phenotype in several species reviewed. Swine and monkey lymphocytes with this phenotype are represented by small resting cells that simultaneou sly express CD4 and CD8 alpha molecules. The available evidence favors the notion that such DP T cells in swine are comprised predominantly of MHC cla ss II restricted memory CD4(+) helper T cells that after activation have ac quired the ability to express the CD8 alpha 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, resilien ce to thymectomy, increase in proportion with age, expression of memory T c ell markers, production of interferon-gamma and localization to inflammator y sites. Some of these characteristics are also descriptive of human and mo nkey CD4/CDs DP T cells. Thus, in swine, humans and monkeys, these phenotyp ically 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. (C) 1999 Elsevier Sci ence B.V. All rights reserved.