Acquisition of T regulatory function in cathepsin L-inhibited T cells by eye-derived CTLA-2alpha during inflammatory conditions.

نویسندگان

  • Sunao Sugita
  • Shintaro Horie
  • Orie Nakamura
  • Kazuichi Maruyama
  • Hiroshi Takase
  • Yoshihiko Usui
  • Masaru Takeuchi
  • Kazumi Ishidoh
  • Masato Koike
  • Yasuo Uchiyama
  • Christoph Peters
  • Yoshimi Yamamoto
  • Manabu Mochizuki
چکیده

Pigment epithelium isolated from the eye possesses immunosuppressive properties such as regulatory T (Treg) cell induction; e.g., cultured retinal pigment epithelium (RPE) converts CD4(+) T cells into Treg cells in vitro. RPE constitutively expresses a novel immunosuppressive factor, CTLA-2alpha, which is a cathepsin L (CathL) inhibitor, and this molecule acts via RPE to induce Treg cells. To clarify CTLA-2alpha's role in the T cell response to RPE in ocular inflammation, we used the experimental autoimmune uveitis (EAU) animal model to examine this new immunosuppressive property of RPE. In EAU models, TGF-beta, but not IFN-gamma inflammatory cytokines, promotes the up-regulation of the expression of CTLA-2alpha in RPE. Similarly, CTLA-2alpha via RPE was able to promote TGF-beta production by the CD4(+) T cells. The RPE-exposed T cells (RPE-induced Treg cells) greatly produced TGF-beta and suppressed bystander effector T cells. There was less expression of CathL by the RPE-exposed T cells, and CathL-inhibited T cells were able to acquire the Treg phenotype. Moreover, CathL-deficient mice spontaneously produced Treg cells, with the increase in T cells potentially providing protection against ocular inflammation. More importantly, CD4(+) T cells from EAU in CathL knockout mice or rCTLA-2alpha from EAU animals were found to contain a high population of forkhead box p3(+) T cells. In both EAU models, there was significant suppression of the ocular inflammation. These results indicate that RPE secretes CTLA-2alpha, thereby enabling the bystander T cells to be converted into Treg cells via TGF-beta promotion.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Acquisition of T Regulatory Function in Cathepsin L-Inhibited T Cells by Eye-Derived CTLA-2 during Inflammatory Conditions

متن کامل

Regulatory T Cells and Myeloid-Derived Suppressor Cells in Patients with Peptic Ulcer and Gastric Cancer

Background: Regulatory T Cells (Tregs) and Myeloid-Derived Suppressor Cells (MDSCs) are two main regulatory cells modulating the immune responses in inflammation and cancer. Objective: To investigate and compare Tregs and MDSCs in peptic ulcer and gastric cancer. Methods: Patients with dyspepsia were selected and divided into three groups of non-ulcer dyspepsia (NUD, n=22), peptic ulcer disease...

متن کامل

T Regulatory Cells Frequency During Maintenance Phase Chemotherapy for Pediatric Acute Lymphoblastic Leukemia

Background: Drugs used in cancer treatment specifically kill T regulatory cells. Objective: To determine different phenotypes of T regulatory cells during the maintenance phase chemotherapy for pediatric acute lymphoblastic leukemia (ALL). Materials: We evaluated the percentages of regulatory T cells by flow cytometry. Soluble CTLA-4 (sCTLA-4) ...

متن کامل

P-212: Association between Polymorphisms of CTLA-4 Gene and Unexplained Recurrent Spontaneous Abortion in An Iranian Population

Background: Unexplained recurrent spontaneous abortion (URSA) has been suggested being associated with the failure of fetal-maternal immunologic tolerance in which the regulatory T lymphocytes (Tregs) play a crucial role. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is expressed transiently on activated T cells and constitutively on Tregs. CTLA-4 interacts with the B7 cell surface molec...

متن کامل

سلول‌های T تنظیمی: انواع، تولید و عملکرد

T lymphocytes have been characterized to different subsets such as cytotoxic T, Thelper1 (Th1), Th2, Th3, Th9, Th17, and regulatory T cells. Each of these subsets have specific function which distinct them from other lymphocytes. Regulatory T lymphocytes are effective cells in immune system that play an important role in cancers, autoimmune and infectious diseases. Two main subsets of regulator...

متن کامل

ذخیره در منابع من

ذخیره در منابع من قبلا به منابع من ذحیره شده

{@ msg_add @}


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of immunology

دوره 183 8  شماره 

صفحات  -

تاریخ انتشار 2009