BTN1A1, the mammary gland butyrophilin, and BTN2A2 are both inhibitors of T cell activation.
نویسندگان
چکیده
Butyrophilin (BTN) genes encode a set of related proteins. Studies in mice have shown that one of these, BTN1A1, is required for milk lipid secretion in lactation, whereas butyrophilin-like 2 is a coinhibitor of T cell activation. To understand these disparate roles of BTNs, we first compared the expression and functions of mouse Btn1a1 and Btn2a2. Btn1a1 transcripts were not restricted to lactating mammary tissue but were also found in virgin mammary tissue and, interestingly, spleen and thymus. In confirmation of this, BTN1A1 protein was detected in thymic epithelial cells. By contrast, Btn2a2 transcripts and protein were broadly expressed. Cell surface BTN2A2 protein, such as the B7 family molecule programmed death ligand 1, was upregulated upon activation of T cells. We next examined the potential of both BTN1A1 and BTN2A2 to interact with T cells. Recombinant Fc fusion proteins of murine BTN2A2 and, surprisingly BTN1A1, bound to activated T cells, suggesting the presence of one or more receptors on these cells. Immobilized BTN-Fc fusion proteins, but not MOG-Fc protein, inhibited the proliferation of CD4 and CD8 T cells activated by anti-CD3. BTN1A1 and BTN2A2 also inhibited T cell metabolism, IL-2, and IFN-gamma secretion. Inhibition of proliferation was not abrogated by exogenous IL-2 but could be overcome following costimulation with high levels of anti-CD28 Ab. These data are consistent with a coinhibitory role for mouse BTNs, including BTN1A1, the BTN expressed in the lactating mammary gland and on milk lipid droplets.
منابع مشابه
Altered expression of Butyrophilin (BTN) and BTN‐like (BTNL) genes in intestinal inflammation and colon cancer
Several Butyrophilin (BTN) and Btn-like (BTNL) molecules control T lymphocyte responses, and are genetically associated with inflammatory disorders and cancer. In this study, we present a comprehensive expression analysis of human and murine BTN and BTNL genes in conditions associated with intestinal inflammation and cancer. Using real-time PCR, expression of human BTN and BTNL genes was analyz...
متن کاملExpression in T Lymphocytes Pathway Signaling and Induces Foxp3 and Phosphatidylinositol 3-Kinase/Akt Butyrophilin Btn2a2 Inhibits TCR Activation
متن کامل
Btn2a2, a T cell immunomodulatory molecule coregulated with MHC class II genes
Evidence has recently emerged that butyrophilins, which are members of the extended B7 family of co-stimulatory molecules, have diverse functions in the immune system. We found that the human and mouse genes encoding butyrophilin-2A2 (BTN2A2) are regulated by the class II trans-activator and regulatory factor X, two transcription factors dedicated to major histocompatibility complex class II ex...
متن کاملIn Vitro Culture and Characterization of a Mammary Epithelial Cell Line from Chinese Holstein Dairy Cow
BACKGROUND The objective of this study was to establish a culture system and elucidate the unique characteristics of a bovine mammary epithelial cell line in vitro. METHODOLOGY Mammary tissue from a three year old lactating dairy cow (ca. 100 d relative to parturition) was used as a source of the epithelial cell line, which was cultured in collagen-coated tissue culture dishes. Fibroblasts an...
متن کاملCanine Mammary Gland Cancer Stem Cell and its Potential Role in Malignant Biologic Behavior
BACKGROUND:Canine mammary gland cancers are the most prevalent malignancies in dogs. There are different challenges regarding management of these cancers in dogs and human, one hypothesis is related to small cellular subset of tumor mass called cancer stem cell. These cells are therapy resistant and cause metastasis and relapse even after primary successful treatment. The well-identified phenot...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 184 7 شماره
صفحات -
تاریخ انتشار 2010