Abstract:
:Heat shock protein (Hsp) 60 is thought to function as endogenous danger signal by activating professional antigen-presenting cells (APC) through toll-like receptor (TLR) 4 and CD14, a mechanism that is also used by bacterial LPS. We recently showed that Hsp60 binds LPS and enhances LPS-induced immune stimulation. On the other hand, we also observed immune stimulation by Hsp60 independent of LPS which was partially mediated by Hsp60-induced IFN alpha. Here, we study the mechanisms involved in immune stimulation mediated by endotoxin-free Hsp60. We show that T cell co-stimulation induced by LPS-free Hsp60 was independent of TLR4 and the TLR-associated myeloide differentiation factor 88-signaling pathway. LPS-free Hsp60 did not induce IL-6, IL-12 or tumor necrosis factor alpha production in APC nor were these cytokines needed for Hsp60-mediated T cell co-stimulation in the absence of LPS. In contrast to endotoxin-free Hsp60, T cell co-stimulation induced by LPS or Hsp60/LPS complexes strictly depended on IL-12 and functional TLR-4. Furthermore, we show that LPS-free Hsp60 enhances IFN alpha expression in APC and that this cytokine represents one important mediator in immune stimulation by Hsp60 in the absence of LPS. Taken together, we provide evidence that endotoxin-free Hsp60 and LPS or Hsp60/LPS complexes employ different signaling mechanisms to transduce co-stimulatory signals.
journal_name
Int Immunoljournal_title
International immunologyauthors
Osterloh A,Veit A,Gessner A,Fleischer B,Breloer Mdoi
10.1093/intimm/dxn003subject
Has Abstractpub_date
2008-03-01 00:00:00pages
433-43issue
3eissn
0953-8178issn
1460-2377pii
dxn003journal_volume
20pub_type
杂志文章abstract::The co-existence of tumor specific immunity with a progressing tumor is observed in a variety of experimental systems and remains one of the major paradoxes of tumor immunology. We now report that a human melanoma cell line (SMC) expressing MHC class II was able to induce clonal anergy in a specific, MHC-restricted CD...
journal_title:International immunology
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pub_type: 杂志文章
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更新日期:2006-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/intimm/10.11.1713
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journal_title:International immunology
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pub_type: 杂志文章,评审
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journal_title:International immunology
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doi:10.1093/intimm/8.7.1045
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journal_title:International immunology
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journal_title:International immunology
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abstract::The thymus leukemia antigens (TL) belong to the MHC class Ib family and can be recognized by CD8-dependent or -independent cytotoxic T lymphocytes (CTL) showing TL, but not H-2, restriction. We previously reported that the CTL epitope is TAP independent and in the present study we further characterize the recognition ...
journal_title:International immunology
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