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 and macrophages, and the increased expression of HLA-DR antigen are consistent with the notion of immune activity in the atherosclerotic plaque. The nature of the causative antigen has not been established although oxidised low density lipoproteins (oxLDL) that accumulate in atherosclerotic plaques could fulfil this role. Here, we report that monocytes play a key role in influencing the fate of purified peripheral human T lymphocytes from healthy donors when the cells are exposed to LDL oxidised under the controlled conditions of water radiolysis. Our data showed that oxLDL generated under these conditions were chemoattractants for T cells. However, they induced a state of apoptosis in T lymphocytes cultured in the absence of monocytes. The extent of apoptosis was related to the degree of oxidation of LDL and the time 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 monocytes 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 oxLDL under similar conditions induced a response that was not different than monocytes exposed to untreated LDL (natLDL) which did not induce T cell proliferation. Fucoidan did not modify the oxLDL-, monocyte-dependent T cell response 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 B7.1 were unchanged. Our data are consistent with the notion that monocytes are critical for T cell survival in the presence of oxLDL and MHC-restricted T cell proliferative response to oxLDL.
Fortun
A
A
Centre de Recherche en Gérontologie et Gériatrie, Institut Universitaire de Gériatrie, Laboratoire de Bio-Gérontologie, Université de Sherbrooke, Quebec, Sherbrooke, Canada J1H 5N4.
Khalil
A
A
Gagné
D
D
Douziech
N
N
Kuntz
C
C
Jay-Gerin
J P
JP
Dupuis
G
G
Fülöp
T
T
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002634:Chemotaxis, Leukocyte; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008285:Major Histocompatibility Complex / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*; D011134:Polysaccharides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D060945:Inducible T-Cell Co-Stimulator Ligand; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; D011134:Polysaccharides; C099252:oxidized low density lipoprotein; C007789:fucoidan