Oxidized phospholipids induce anergy in human peripheral blood T cells.
Lipids are key regulators of immune responses. In this study we investigated the direct impact of oxidized phospholipids (ox-PL) on T cell activation and function. We could demonstrate that ox-PL strongly inhibit proliferation of purified human T cells induced with anti-CD3/CD28 or anti-CD3/CD63 mAb, whereas proliferation of naive T cells from human cord blood was not affected by ox-PL. Unoxidized phospholipids showed no such effect. Inhibition of T cell proliferation by ox-PL was not due to cell death. Moreover, T cell proliferation triggered by PMA/ionomycin activation was not diminished by ox-PL. T cells activated in the presence of ox-PL produced and released low amounts of IFN-gamma and IL-2, whereas IL-4 was only slightly diminished. Ox-PL prevented the expression of de novo synthesized activation markers (CD25, MHC class II) but not expression of CD63 or CD69. We further observed that T cells stimulated in the presence of ox-PL are poorly cytotoxic T cells. Most importantly, T cells activated in the presence of ox-PL failed to proliferate in response to restimulation. This hypo-proliferative state was accompanied with an up-regulation of early growth response gene 3 and Casitas B-lineage lymphoma protein B. Taken together, our results demonstrate that ox-PL are potent and specific regulators of T cell activation and function.
Seyerl
Maria
M
Institute of Immunology, Medical University of Vienna, Vienna, Austria.
Blüml
Stefan
S
Kirchberger
Stefanie
S
Bochkov
Valery N
VN
Oskolkova
Olga
O
Majdic
Otto
O
Stöckl
Johannes
J
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D051776:Early Growth Response Protein 3 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D010084:Oxidation-Reduction; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000494:pharmacology; D010718:Phosphatidylserines / Q000737:chemistry / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000737:chemistry / Q000494:pharmacology; D010743:Phospholipids / Q000737:chemistry / Q000494:pharmacology*; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
C400184:1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine; C400185:1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphorylcholine; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016207:Cytokines; C079945:EGR3 protein, human; D000949:Histocompatibility Antigens Class II; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D010742:Phospholipid Ethers; D010743:Phospholipids; D051776:Early Growth Response Protein 3; D050721:Proto-Oncogene Proteins c-cbl