Modulation of cellular immunity by antibodies against calreticulin

Although caltreticulin (CRT) is mainly a residential ER protein, it is also expressed on the membrane surface of various types of cells exhibiting multiple functions. We report here that intraperitoneal administration of a soluble recombinant CRT fragment (rCRT/39‐272) led to a substantial decrease...

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Bibliographic Details
Published in:European journal of immunology 2012-09, Vol.42 (9), p.2419-2430
Main Authors: Qiu, Xiang, Hong, Chao, Zhong, Zhaoyan, Li, Yue, Zhang, Tengteng, Bao, Wanrong, Xiong, Sidong, Gao, Xiao‐Ming
Format: Article
Language:English
Subjects:
Animals
Antibodies - immunology
Anti‐CRT antibodies
Calreticulin
Calreticulin - immunology
Cell Proliferation
Female
Hemocyanins - immunology
Hypersensitivity, Delayed - immunology
Immunity, Cellular - immunology
Immunoregulation
Interferon-gamma - immunology
Interleukin-4 - immunology
Lymph Nodes - immunology
Lymphocyte Activation - immunology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Phosphorylation - immunology
Proto-Oncogene Proteins c-akt - immunology
Recombinant Proteins - immunology
T-Lymphocytes - immunology
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Summary:Although caltreticulin (CRT) is mainly a residential ER protein, it is also expressed on the membrane surface of various types of cells exhibiting multiple functions. We report here that intraperitoneal administration of a soluble recombinant CRT fragment (rCRT/39‐272) led to a substantial decrease in delayed type hypersensitivity (DTH) responses in BALB/c mice and EAE in C57BL/6 mice. In the recall response against keyhole limpet hemocyanin (KLH) in vitro, draining lymph node cells from the rCRT/39‐272‐treated mice produced less IFN‐γ but more IL‐4 as compared with the cells from the control group. The immunomodulating effect of intraperitoneally administered rCRT/39‐272 was attributed to anti‐CRT Abs thereby induced, because, in passive transfer experiments, the CRT‐specific antiserum could suppress DTH in BALB/c mice. B‐cell‐deficient μMT mice were not susceptible to rCRT/39‐272‐mediated DTH suppression. Furthermore, CRT appears on the surface of murine T cells soon after activation and remains detectable (at relatively low level) by flow cytometry for approximately 5 days in vitro. Anti‐CRT Abs were able to inhibit AKT phosphorylation, proliferation, and cytokine production by activated murine T cells. We propose that cell surface CRT could play a role in the function of effector T cells and may be considered a target for immunological manipulation.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201142320