Tolerization with Hsp65 induces protection against adjuvant-induced arthritis by modulating the antigen-directed interferon-gamma, interleukin-17, and antibody responses.
Tolerization with Hsp65 induces protection against adjuvant-induced arthritis by modulating the antigen-directed interferon-gamma, interleukin-17, and antibody responses.
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DOI：
10.1002/art.24139
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发表时间：
2009-01
影响因子：
--
通讯作者：
Moudgil, Kamal D.
中科院分区：
文献类型：
--
作者：
Satpute, Shailesh R.;Rajaiah, Rajesh;Polumuri, Swamy K.;Moudgil, Kamal D.
Pre-treatment of Lewis (LEW) rats with soluble mycobacterial hsp65 (Bhsp65) affords protection against subsequently induced adjuvant arthritis (AA). This study was aimed at unraveling the mechanisms underlying the Bhsp65-induced protection against arthritis using contemporary immune parameters. LEW rats were given 3 i.p. injections of Bhsp65 in solution prior to induction of AA with heat-killed Mycobacterium tuberculosis (Mtb). Thereafter, the Bhsp65-specific T cell proliferative, cytokine, and antibody responses were tested in tolerized rats. The roles of anergy and indoleamine 2,3 dioxygenase (IDO)-tryptophan pathway in tolerance induction were assessed along with monitoring the frequency and suppressive function of CD4+Foxp3+ T regulatory cells (Treg). Also tested was the effect of Bhsp65-tolerization on T cell responses to AA-related Bhsp70, Bhsp10 and rat hsp65 (Rhsp65). The AA-protective effect of Bhsp65-induced tolerance was associated with significantly reduced T cell proliferative response to Bhsp65, which was reversible by IL-2, indicating anergy induction. There was increased production of IFN-γ but not IL-4/IL-10, with concurrent downregulation of IL-17 expression by Bhsp65-primed T cells. Neither the frequency nor the suppressive activity of CD4+FoxP3+ T cells changed following tolerization, but the level of serum anti-Bhsp65 antibodies was increased. However, no evidence was found for the roles of IDO or cross-tolerance to Bhsp70, Bhsp10 or Rhsp65. Tolerization with soluble Bhsp65 leads to suppression of IL-17, anergy induction, and enhanced production of anti-Bhsp65 antibodies, which play a role in protection against AA. These results are of relevance to developing effective immunotherapeutic approaches for autoimmune arthritis.
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影响因子：
15.3
作者：
Moudgil, K D;Chang, T T;Eradat, H;Chen, A M;Gupta, R S;Brahn, E;Sercarz, E E
通讯作者：
Sercarz, E E
影响因子：
4.4
作者：
Durai, M;Gupta, RS;Moudgil, KD
通讯作者：
Moudgil, KD
影响因子：
--
作者：
Chu, Cong-Qiu;Swart, David;Elkon, Keith B.
通讯作者：
Elkon, Keith B.
影响因子：
4.6
作者：
Esaguy, N;Aguas, AP
通讯作者：
Aguas, AP
DOI：
10.1084/jem.189.9.1363
发表时间：
1999-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Munn DH;Shafizadeh E;Attwood JT;Bondarev I;Pashine A;Mellor AL
通讯作者：
Mellor AL