Search

The Naive/Memory T Cell paradigm was used to determine how aging affects the cellular and molecular mechanisms in T cell-dependent immunity. Naive T cells express early response genes, after an encounter with antigen, including those behind T cell growth factor, namely, interleukin-2 (IL-2) and the IL-2 receptor chains. The latter pushes activated cells to proliferate and separate into effector T cells, yielding more differentiated, antigen-specific T cells known as memory cells. These memory T cells can express increased levels and a wider range of lymphokines than the naive T cells because of their differentiated state.

The investigation of two distinct molecular weight forms of human ABCB6 was observed to be localized to both the outer mitochondrial membrane and the plasma membrane and plays a functional role in the plasma membrane.

Abstract: The impact of CD28 ligation upon CD4+ and CD8+ T lymphocyte proliferation and cytokine production was assessed. Although costimulation increased the proliferative response of both T cell subsets, cytokine production was most markedly increased in the CD4+ subset, as evidenced by a 40-fold increase in interleukin-2 (IL-2), a 14-fold increase in interleukin-3 (IL-3) and 5-fold increases in interferon γ and GM-colony-stimulating factor (CSF) production. The CD8+ T cell response to CD28 ligation was less marked, maxima being a 5-fold increase in IL-2 production and 2-fold increases in IL-3 and GM-CSF production. Resolution of CD4+ and CD8+ T cells into their CD44lo (naïve) and CD44hi (memory/effector) subsets revealed that naïve CD4+ T cells were the most CD28-responsive subsets. CD28-mediated costimulation promotes distinct differentiation programs in CD4+ versus CD8+ T cells. [Copyright &y& Elsevier]

T cell proliferative responses decrease with age, but the mechanisms responsible are unknown. We examined the impact of age on memory and naive CD4+ T cell entry and progression through the cell cycle using acridine orange to identify cell cycle stage. For both subsets, fewer stimulated cells from old donors were able to enter and progress through the first cell cycle, with an increased number of cells arrested in G0 and fewer cells in post G0 phases. The number of dead cells as assessed by sub-G0 DNA was also significantly greater in the old group. CD4+ T cells from old mice also exhibited a significant reduction in clonal history as assessed by CFSE staining. This was associated with a significant decline in cyclin D2 mRNA and protein. We propose that decreases in cyclin D2 are at least partially responsible for the proliferative decline found in aged CD4+ T cells. [Copyright &y& Elsevier]