Two different modes of costimulation predispose human T lymphocytes to differential responses in the presence of HDL or oxidized LDL

In addition to levels of high-density lipoprotein (HDL), oxidized (ox) low-density lipoprotein (LDL), the inflammatory process and certain genetic factors, T cells are crucial for expansion of atherosclerotic plaque. The interrelationships among these influences are still being defined. Here, we examined how HDL and oxLDL affect T cell function. T cells require two activation signals to achieve functional activity. The first signal is specific and is delivered by appropriately presented antigen. The second (costimulatory) signal can be received through any of several T cell surface proteins, the most widely studied of which are CD28 and LFA-1. We have identified ICAM-1, resident on T cells, as a costimulatory protein. Here, we describe differential effects when T cells were costimulated through either LFA-1 or ICAM-1 in the presence of HDL or oxLDL. In general, T cells costimulated through either LFA-1 or ICAM-1 in the presence of oxLDL were predisposed to a decrease in proliferation and increased apoptosis, although ICAM-1-costimulated cells were protected from apoptosis induced by lower levels of oxLDL. T cell subsets also were examined. In the presence of HDL, CD8(+) T cells increased proliferation when costimulated through LFA-1. HDL exerted no effect on proliferation of CD4(+) T cells whereas proliferation decreased in the presence of oxLDL. Naïve T cells proliferated better in response to costimulation through LFA-1 in the presence of HDL but proliferation of effector/memory cells was not altered in the presence of HDL. When T cells were costimulated through LFA-1, in the presence of either HDL or oxLDL synthesis of Th-1 but not Th-2 cytokines was increased. T cells costimulated through ICAM-1 increased Th-1 but not Th-2 cytokines but this was not altered in the presence of HDL or oxLDL. Thus, the nature of costimulation seems to influence T cell responses in the presence of the lipoproteins.