Monocytes influence the fate of T cells challenged with oxidised low density lipoproteins towards apoptosis or MHC-restricted proliferation

Atherosclerosis has been implicated in myocardial infarction. stroke and a host of cardiovascular diseases. The presence of activated T lymphocytes an d macrophages, and the increased expression of HLA-DR antigen are consisten t with the notion of immune activity in the atherosclerotic plaque. The nat ure of the causative antigen has not been established although oxidised low density lipoproteins (oxLDL) that accumulate in atherosclerotic plaques co uld fulfil this role. Here, we report that monocytes play a key role in inf luencing the fate of purified peripheral human T lymphocytes from healthy d onors when the cells are exposed to LDL oxidised under the controlled condi tions of water radiolysis. Our data showed that oxLDL generated under these conditions were chemoattractants for T cells. However, they induced a stat e of apoptosis in T lymphocytes cultured in the absence of monocytes. The e xtent of apoptosis was related to the degree of oxidation of LDL and the ti me of T cell exposure to oxLDL. OxLDL-dependent apoptosis did not involve a scavenger-like receptor. CD4(+) cells were more sensitive to the apoptotic effect of oxLDL than CD8(+) cells. OxLDL-primed (12 h) autologous monocyte s triggered a robust proliferation of T lymphocytes cultured in the absence of oxLDL. The strength of T cell stimulation was related to the degree of oxidation of the LDL used in priming. Heterologous monocytes exposed to oxL DL under similar conditions induced a response that was not different than monocytes exposed to untreated LDL (natLDL) which did not induce T cell pro liferation. Fucoidan did not modify the oxLDL-, monocyte-dependent T cell r esponse to proliferation. suggesting that a scavenger-like receptor was not involved. The expression of the HLA-DR marker and the B7.2 protein were up -regulated in monocytes exposed to oxLDL but not to natLDL. The levels of B 7.1 were unchanged. Our data are consistent with the notion that monocytes are critical for T cell survival in the presence of oxLDL and MHC-restricte d T cell proliferative response to oxLDL. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.