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 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.
Department of Immunology, Peking University Health Science Center, Beijing, China.
Xiang
X
Qiu
Chao
C
Hong
Zhaoyan
Z
Zhong
Yue
Y
Li
Tengteng
T
Zhang
Wanrong
W
Bao
Sidong
S
Xiong
Xiao-Ming
XM
Gao
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D037282:Calreticulin / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D037282:Calreticulin; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D006433:Hemocyanins; D051057:Proto-Oncogene Proteins c-akt; C032808:keyhole-limpet hemocyanin