Elevated intracellular glutathione levels in CD4 + T cells of BB rats

Abstract

GLUTATHIONE (GSH) is a dominant intracellular redox buffering compound which is essential for survival and several functions of peripheral T cells. It is the main free radical scavenger in T cells, protecting them from oxidative stress-induced and antigen-driven apoptosis. 1,2 In addition, GSH is important for T cell proliferation, 3,4 mitogen-induced activation, 5 cytotoxicity, 6 interleukin-2 (IL-2)-dependent DNA synthesis, 7 and it enhances IL-2 binding, internalization, and degradation by cytotoxic T cells. 8 GSH depletion in vitro was shown to inhibit mouse T cell proliferation; however, this was shown to exist predominantly for CD8 + T cells and to a much lesser extent for CD4 + T cells, thereby markedly increasing the CD4/CD8 ratio in GSH-depleted cultures. 9 Peripheral T cells of the T lymphocytopenic diabetes-prone BB (DPBB) rat display many phenotypic and functional abnormalities. After thymic emigration, a majority of these cells dies very rapidly 10,11 by apoptosis (S. Ramanathan, this issue). The remaining cells proliferate poorly on allogenic and mitogenic stimulation, 12,13 and IL-2 production has been reported to be decreased. 14 CD8 + T cells are virtually absent in DPBB rats, 15 which is partly due to a more severely reduced life span for CD8 + than for CD4 + T cells, 11 and cytotoxic T lymphocytes exhibit reduced cytotoxic capacity. 16,17 It is presently largely unknown why T cells in DPBB rats display these abnormalities; however, it can be hypothesized that they are a reflection of decreased intracellular GSH levels. For this reason, we investigated whether peripheral T cells in the DPBB rat, and CD8 + T cells in particular, have reduced intracellular GSH levels.