Late expression of granulysin by microbicidal cd4(+) t cells requires pi3k- and stat5-dependent expression of il-2r beta that is defective in hiv-infected patients | |
Zheng, Chun Fu1,3; Jones, Gareth J.1; Shi, Meiqing1; Wiseman, Jeremy C. D.1; Marr, Kaleb J.1; Berenger, Byron M.1; Huston, Shaunna M.1; Gill, M. John1; Krensky, Alan M.4; Kubes, Paul1,2 | |
刊名 | Journal of immunology |
2008-06-01 | |
卷号 | 180期号:11页码:7221-7229 |
ISSN号 | 0022-1767 |
通讯作者 | Mody, christopher h.(cmody@ucalgary.ca) |
英文摘要 | Granulysin is a cytolytic effector molecule used by lymphocytes to kill tumor and microbial cells. regulation of granulysin production is complex. a significant delay (5 days) following stimulation of cd4(+) t cells with il-2 occurs before granulysin is produced. unfortunately, the mechanisms responsible for this delay are unknown. we have recently demonstrated that granulysin-mediated killing of cryptococcus neoformans by cd4(+) t cells is defective during hiv infection. this is because cd4(+) t cells from hiv-infected patients fail to produce granulysin in response to il-2 activation. the present studies examined the mechanism of delayed production of granulysin and the mechanism of the defect in hiv patients. we demonstrate that il-2 initially requires both stat5 and pi3k activation to increase expression of il-2r beta, produce granulysin, and kill c. neoformans. the increased expression of il-2r beta precedes granulysin, and preventing the increased expression of il-2r beta using small interfering rna knockdown abrogates granulysin expression. moreover, following the increased expression of il-2r beta, blocking subsequent signaling by il-2 using il-2r beta-specific blocking abs abrogates expression of granulysin. finally, cd4(+) t cells from hiv-infected patients, who are defective in both stat5 and pi3k signaling, fail to express il-2r beta and fail to produce granulysin. these results suggest that il-2 signals via pi3k and stat5 to increase expression of il-2r beta, which in turn is required for production of granulysin. these results provide a mechanism to explain the "late" production of granulysin during normal t cell responses, as well as for defective granulysin production by cd4(+) t cells in hiv-infected patients. |
WOS关键词 | BLOOD MONONUCLEAR-CELLS ; RECEPTOR-GAMMA CHAIN ; CRYPTOCOCCUS-NEOFORMANS ; INTERLEUKIN-2 RECEPTOR ; IL-2 RECEPTOR ; BETA-CHAIN ; PHOSPHATIDYLINOSITOL 3-KINASE ; SIGNALING PATHWAYS ; TRANSCRIPTION FACTORS ; HUMAN-LYMPHOCYTES |
WOS研究方向 | Immunology |
WOS类目 | Immunology |
语种 | 英语 |
出版者 | AMER ASSOC IMMUNOLOGISTS |
WOS记录号 | WOS:000257507300018 |
内容类型 | 期刊论文 |
URI标识 | http://www.corc.org.cn/handle/1471x/2375459 |
专题 | 武汉病毒研究所 |
通讯作者 | Mody, Christopher H. |
作者单位 | 1.Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada 2.Univ Calgary, Dept Physiol & Biophys, Calgary, AB T2N 4N1, Canada 3.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Peoples R China 4.Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA |
推荐引用方式 GB/T 7714 | Zheng, Chun Fu,Jones, Gareth J.,Shi, Meiqing,et al. Late expression of granulysin by microbicidal cd4(+) t cells requires pi3k- and stat5-dependent expression of il-2r beta that is defective in hiv-infected patients[J]. Journal of immunology,2008,180(11):7221-7229. |
APA | Zheng, Chun Fu.,Jones, Gareth J..,Shi, Meiqing.,Wiseman, Jeremy C. D..,Marr, Kaleb J..,...&Mody, Christopher H..(2008).Late expression of granulysin by microbicidal cd4(+) t cells requires pi3k- and stat5-dependent expression of il-2r beta that is defective in hiv-infected patients.Journal of immunology,180(11),7221-7229. |
MLA | Zheng, Chun Fu,et al."Late expression of granulysin by microbicidal cd4(+) t cells requires pi3k- and stat5-dependent expression of il-2r beta that is defective in hiv-infected patients".Journal of immunology 180.11(2008):7221-7229. |
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