ABNORMAL THYMOCYTE SUBSET DISTRIBUTION AND DIFFERENTIAL REDUCTION OF CD4(-CELL SUBSETS DURING PERIPHERAL MATURATION IN DIABETES-PRONE BIOBREEDING RATS() AND CD8(+) T)

In this study we quantified CD8(+) and CD4(+) T cells in T lymphocytop enic BB rats as compared with control rats at given stages along the m aturational pathway from immature thymocytes to mature peripheral T ce lls. Our results show that BB rats exhibit abnormal thymocyte subset d istribution. Numbers of mature TCR(high)/CD4(-)8(+) thymocytes, and al so their TCR(high)/CD4(+)8(+) precursors were decreased, as were level s of CD8 expression on all thymocyte subsets investigated. By analogy with mouse thymocyte development, these findings suggest a decreased e fficiency for positive selection of CD8 precursors in BB rats. Further more, as related to the number of available mature TCR(high) Single po sitive thymocytes, numbers of CD4(+) and CD8(+) T cells most recently migrated from the thymus were severely decreased in BB blood, indicati ng either reduced thymic output or rapid cell death after migration. S ubsequently, in peripheral blood and cervical lymph nodes, a 95% decre ase of CD8(+) and a 50 to 80% decrease of CD4(+) T cells were demonstr ated upon maturation from recent thymic migrants to mature peripheral T cells, leaving the BB rat with a severely reduced T cell population, consisting of CD4(+) T cells and a minute population of CD8(+) T cell s. The vast majority of the latter was found to have an immature perip heral phenotype. Possible consequences of our findings for the generat ion of autoreactive CD8(+) T cells are discussed.