title: Immunosuppressive effect of angiotensin receptor blocker on stimulation of mice CTLs by angiotensin II.
abstract: While angiotensin II, which is produced by the renin-angiotensin-aldosterone system, is considered to be the major regulator molecule that controls both the blood pressure and fluid system, there is an increasing body of evidence that this bioactive peptide and its receptor might also contribute to the immune system. However, there are few details known about the direct effect that angiotensin type I receptors (AT1R) have on the cytotoxic T cell (CTL). To clarify the relationship between angiotensin II and its CTL receptor, we used murine splenic and antigen-specific CTLs. Murine CTLs constantly expressed AT1R, with the activation of the AT1R expression strengthened by both anti-CD3 Ab and the use of an antigen-specific methodology. Moreover, the production of IFN-gamma and TNF-alpha through CTL stimulation can be inhibited by the selective AT1R inhibitor, Losartan. In particular, the TNF-alpha production from activated CTL that had been magnified by angiotensin II, was nullified by the AT1R inhibitor. However, a cytotoxic assay indicated it did not have any effect on the cognate interaction of the CTLs. In addition, the antigen-specific CTL induction by immunization with the CTL antigenic peptide was reduced by angiotensin II type 1 receptor blocker (ARB) in vivo. These findings suggest that ARBs might have the ability to suppress excessive antigen-specific activation and induction of CTLs promoted by angiotensin II.
authors.affiliation: Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Maeda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Okazaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Takako
authors.initials: T
authors.lastname: Kitazono
authors.forename: Masaomi
authors.initials: M
authors.lastname: Yamasaki
authors.forename: François A
authors.initials: FA
authors.lastname: Lemonnier
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ozaki
mesh_terms: D000804:Angiotensin II / Q000276:immunology / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics; D015789:HLA-A2 Antigen / Q000235:genetics; D064532:Histocompatibility Antigen H-2D; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D015789:HLA-A2 Antigen; D064532:Histocompatibility Antigen H-2D; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D007371:Interferon-gamma; D019808:Losartan