Therapeutic potential for blockade of the CD40 ligand, gp39
Therapeutic potential for blockade of the CD40 ligand, gp39
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阻断 CD40 配体 gp39 的治疗潜力
DOI：
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发表时间：
1996
影响因子：
9.1
通讯作者：
R. Noelle
中科院分区：
文献类型：
--
作者：
J. Buhlmann;R. Noelle
结论越来越多的证据支持gp 39-CD 40相互作用在体液和细胞免疫应答的发展中起关键作用。已经表明，gp 39和CD 40对于抗体应答和记忆B细胞的发育和产生是关键的。这种配体受体对参与其他类型的免疫反应的证据不断出现。在GVHD系统中的实验以及B细胞在抗gp 39存在下耐受T细胞的能力表明，gp 39和CD 40对于细胞免疫应答的产生也是重要的。对细胞免疫应答的影响可能是通过控制适当的抗原呈递和刺激所必需的共刺激分子。已经表明，CD 40可以控制几种类型的抗原呈递细胞上的共刺激分子表达;这可能是调节细胞呈递抗原能力的关键步骤。gp 39和CD 40在调节细胞因子、一氧化氮产生和细胞外渗中的作用刚刚被阐明，但这可能是gp 39可能具有调节作用的另一层免疫应答。因此，由于gp 39-CD 40相互作用在免疫应答的传出臂和传入臂中都是至关重要的，因此这种配体-受体对是非常有吸引力的治疗靶点。阻断这种相互作用可能会提高同种异体移植物和移植物的存活率，并可能抑制广泛的自身免疫性疾病。
ConclusionsThere is mounting evidence supporting a critical role for gp39-CD40 interactions in the development of both humoral and cellular immune responses. It has been shown that gp39 and CD40 are critical for the development and generation of antibody responses and memory B cells. Evidence for this ligand receptor pair being involved in other types of immune responses is constantly emerging. Experiments in the GVHD system as well as the ability of B cells to tolerize T cells in the presence of anti-gp39 suggest that gp39 and CD40 are also important for the generation of cellular immune responses. The effect on cellular immune responses may be through the control of costimulatory molecules necessary for proper antigen presentation and stimulation. It has been shown that CD40 can control costimulatory molecule expression on several types of antigen-presenting cells; this may be a critical step in the regulation of a cell's ability to present antigen. The role of gp39 and CD40 in the regulation of cytokines, nitric oxide production, and extravasation of cells is just being elucidated but this is potentially yet another tier of immune responses upon which gp39 may have a regulatory effect. Thus, because gp39-CD40 interactions are critical in both the efferent and the afferent arms of the immune response, this ligand-receptor pair is a highly attractive therapeutic target. Blockade of this interaction may lead to enhanced survival of allografts and transplants as well as potentially being able to inhibit a wide spectrum of autoimmune diseases.
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一氧化氮在移植物抗宿主疾病中的免疫抑制作用的表征。
DOI：
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发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hoffman,RA;Langrehr,JM;Wren,SM;Dull,KE;Ildstad,ST;McCarthy,SA;Simmons,RL
通讯作者：
Simmons,RL
B 细胞处理并呈递狼疮自身抗原，启动自身免疫 T 细胞反应。
DOI：
--
发表时间：
1994
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Mamula,MJ;Fatenejad,S;Craft,J
通讯作者：
Craft,J
DOI：
10.1172/jci117453
发表时间：
1994-09
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
F. H. Durie;A. Aruffo;J. Ledbetter;K. M. Crassi;W. Green;L. Fast;R. Noelle
通讯作者：
F. H. Durie;A. Aruffo;J. Ledbetter;K. M. Crassi;W. Green;L. Fast;R. Noelle
DOI：
10.1073/pnas.92.10.4342
发表时间：
1995-05-09
影响因子：
11.1
作者：
KARMANN, K;HUGHES, CCW;POBER, JS
通讯作者：
POBER, JS
DOI：
10.1073/pnas.91.25.12135
发表时间：
1994-12-06
影响因子：
11.1
作者：
CASTIGLI, E;ALT, FW;GEHA, RS
通讯作者：
GEHA, RS