Role of CD28/B7 costimulation and IL-12/IL-10 interaction in the radiation-induced immune changes

被引：103

作者：

Liu S.-Z. ^{[1
]}

Jin S.-Z. ^{[1
]}

Liu X.-D. ^{[1
]}

Sun Y.-M. ^{[1
]}

机构：

[1] Immunology Lab. Radiology Res. Unit, Ministry of Health, Jilin University, Changchun 130021

来源：

BMC Immunology | / 2卷 / 1期

关键词：

Peritoneal Macrophage; Proliferative Response; High Dose Radiation; Splenic Lymphocyte; Immunological Change;

D O I：

10.1186/1471-2172-2-8

中图分类号：

学科分类号：

摘要：

Background: The present paper aims at studying the role of B7/CD28 interaction and related cytokine production in the immunological changes after exposure to different doses of ionizing radiation. Results: The stimulatory effect of low dose radiation (LDR) on the proliferative response of lymphocytes to Con A was found to require the presence of APCs. The addition of APCs obtained from both low- and high-dose-irradiated mice to splenic lymphocytes separated from low-dose-irradiated mice caused stimulation of lymphocyte proliferation. B7-1/2 expression on APCs was upregulated after both low and high doses of radiation. There was up-regulation of CD28 expression on splenic and thymic lymphocytes after LDR and its suppression after high dose radiation (HDR), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression showed changes in the opposite direction. IL-12 secretion by macrophages was stimulated after both low and high doses of radiation, but IL-10 synthesis by splenocytes was suppressed by low dose radiation and upregulated by high dose radiation. Conclusion: The status of CD28/CTLA-4 expression on T lymphocytes in the presence of upregulated B7 expression on APCs determined the outcome of the immune changes in response to radiation, i.e., up-regulation of CD28 after LDR resulted in immunoenhancement, and up-regulation of CTLA-4 associated with down-regulation of CD28 after HDR led to immunosuppression. Both low and high doses of radiation up-regulated B7-1/2 expression on APCs. After LDR, the stimulated proliferative effect of increased IL-12 secretion by APCs, reinforced by the suppressed secretion of IL-10, further strengthened the intracellular signaling induced by B7-CD28 interaction. © 2001 Liu et al; licensee BioMed Central Ltd.

引用

共 20 条

[1] Liu S.Z., Bai O., On mechanistic studies of immune responses following low dose ionizing radiation, International Meeting on Biological Effects of Low Dose Radiation, pp. 129-135, (2000)
[2] Liu S.Z., Bai O., Chen D., Ye F., Genes and protein molecules involved in the cellular activation induced by low dose radiation, Radia. Res. Radiat. Proc., 18, pp. 175-186, (2000)
[3] Liu S.Z., Multilevel mechanisms of stimulatory effect of low dose radiation on immunity, Low Does Irradiation and Biological Defense Mechanisms, pp. 225-232, (1992)
[4] Liu S.Z., Xie F., Involvement of the Ca2+ -protein kinase C and adenylate cyclase signal pathways in the activation of thymocytes in response to whole-body irradiation with low dose X-rays, Chin. Med. Sci. J., 15, pp. 1-7, (2000)
[5] Liu S.Z., Liu W.H., Sun J.B., Radiation Hormesis: Its expression in the immune system, Health Physics, 52, pp. 579-583, (1987)
[6] Liu S.Z., Su X., Zhang Y.C., Zhao Y., Signal transduction in lymphocytes after low dose radiation, Int. J. Occup. Med. Toxicol., 3, pp. 107-117, (1994)
[7] James S.J., Makinodan T., T cell proliferation in normal and autoimmune-prone mice after extended exposure to low doses of ionizing radiation and/or caloric restriction, Int. J. Radiat. Biol., 53, pp. 137-152, (1988)
[8] Greenfield E.A., Nguyen K.A., Kuchroo V.K., CD28/B7 costimulation: A review, Crit. Rev. Immunol., 18, pp. 389-418, (1988)
[9] Agadjanyan M.G., Kim J.J., Trivedi N., Wilson D.M., Monzavi-Karbassi B., Morrison L.D., Nottingham L.K., Dentchev T., Tsai A., Dang K., Chalian A.A., Maldonado M.A., Williams W.V., Weiner D.B., CD86 (B7-2) can function to drive MHC-restricted antigen-specific CTL responses in vivo, J. Immunol., 162, pp. 3417-3427, (1999)
[10] Kuhns M.S., Epshteyn V., Sobel R.A., Allison J.P., Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates the size, reactivity, and function of a primed pool of CD4+ T cells, Proc. Natl. Acad. Sci. USA, 97, pp. 12711-12716, (2000)

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