Tolerance to an Arthritogenic T‐cell Epitope of HSP65 and the Regulation of Experimental Arthritis
Tolerance to an Arthritogenic T‐cell Epitope of HSP65 and the Regulation of Experimental Arthritis
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HSP65 致关节炎 T 细胞表位的耐受性和实验性关节炎的调节
DOI：
10.1111/j.1749-6632.1996.tb21163.x
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发表时间：
1996
影响因子：
5.2
通讯作者：
W. Eden
中科院分区：
文献类型：
--
作者：
B. Prakken;R. Zee;S. Anderton;P. Kooten;W. Kuis;W. Eden
Adjuvant arthritis (AA) is an extensively studied form of experimental arthritis resembling rheumatoid arthritis in a number of pathological aspects. It can be induced in susceptible (Lewis) rats by immunization with mycobacterial antigens. From several experiments it can be concluded that T-cell responses to hsp’s play an important immunomodulatory role in the induction AA. First it was shown that AA can be passivily transfered by T cells alone from diseased rats to syngeneic disease-free animals.’ Fuxtherniore passive transfer of a T-cell clone recognizing the nonconserved 180188 amino acid sequence in mycobacterial hsp65 was found to induce AA.z3 This T-cell clone also responded to cartilage proteoglycan but not to rat hsp60. The clone therefore showed tliat although self-cross-reactive or “mimicry” T cells are able to induce overt autoimmune disease, this was not related to the conserved nature of hsp’s. Several studies have shown that it is possible to induce antigen-specific T-cell tolerance in experimental autoimmune models! Most evidence so far has been collected in the model of experimental allergic encephalomyelitis (EAJZ). EAE is a demyelinating autoimmune disease caused by CD4’ T cells specific for myelin basic protein (MBP). It can be induced in susceptible animals by immunization with MBP in CFA. However, oral administration of MBP protects animals from developing E M . Protection can be established by adoptive transfer of CD8+ T cells, capable of producing TGF-P when stimulated with the relevant antigen^.^ Encephalogenic epitopes of MBP have been characterized, and nasal inhalation of the immunodominant epitope on MBP has also led to protection. In the present study we investigated whether tolerance could be induced similarly to the AA-related immunodominant epitope and whether this would lead to protection against AA, a disease induced by an antigen as complex as whole mycobacteria. Two 15-mer peptides containing the individual mycobacterial hsp65 sequences 176190 (M36) and 211-225 (M43) were used. M36 contains the epitope 180-188 recognized by the arthritogenic T-cell clone, A2b. Furthermore, it is the immunodominant T-cell epitope after induction of arthritis in AA.6 M43 is a codominant epitope both after induction
