Adjuvant arthritis and immunity to the mycobacterial 65 kDa heat shock protein

Abstract

The mycobacterial 65 kDa heat shock protein (HSP65) is of critical significance in the model of adjuvant arthritis (AA). Arthritogenic and protective T cell clones obtained from arthritic rats recognized the 180-188 sequence of HSP65. Previous reports have shown that administration of HSP65 prior to disease induction led to resistance to arthritis in the AA model and in several other models of experimental arthritis. Here, we report the development of immunity to HSP65 and the critical 180-188 epitope during the course of AA. Following Mycobacterium tuberculosis (MT) immunization both antibodies and T cell responses to HSP65 were detected. Proliferative responses to the 180-188 epitope were seen exclusively in the local draining lymph node cells at day 14 after immunization. The anatomical distribution and course of T cell responses to HSP65 and its 180-188 epitope are compatible with T cell regulated control of the disease. Although lower HSP65 antibody levels were observed in the animals with severe arthritis, in individual animals no evidence was obtained for a relationship between development of HSP65 humoral immunity and arthritis severity. Nevertheless, during disease exacerbation, elicited by HSP65 immunization during disease development, elevated T cell responses against HSP65 and its 180-188 epitope were found. In contrast, we obtained evidence that successful transfer of arthritis resistance to naive recipients depends on the transfer of HSP65 specific T cells. On the basis of these results, it seems that HSP65 plays a crucial role in the T cell regulatory events involved in both the induction of, and protection against, AA.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced expression of heat shock protein 70 (hsp70) and heat shock factor 1 (HSF1) activation in rheumatoid arthritis synovial tissue. Differential regulation of hsp70 expression and hsf1 activation in synovial fibroblasts by proinflammatory cytokines, shear stress, and antiinflammatory drugs.

“…The arthritogenic role of mycobacterial hsp65 in adjuvant arthritis of rats is well established (1,3), whereas the role of hsp in human RA is seen controversially, although T cell and antibody autoimmunities against hsp60 have been described in RA (52)(53)(54). In adjuvant arthritis the immune reactions against hsp60 have been shown to be protective (55), which is corroborated by recent data from children with juvenile chronic polyarthritis (56,57). Whether hsp70 itself is targeted by the autoimmune response in RA remains to be clarified.…”

Autoreactivity to human heat‐shock protein 60 predicts disease remission in oligoarticular juvenile rheumatoid arthritis

“…It can be induced in susceptible (Lewis) rats by immunization with mycobacterial antigens (20). From several experiments, it can be concluded that T cell responses to HSP play an important immunomodulatory role in the induction of AIA (21). First, it was shown that AIA can be passively transferred by T cells from diseased rats to syngeneic disease-free animals (22).…”

The stressed synovium

“…Overexpression of HSP60 might also explain the development of an autoimmune response to this protein because overexpression might go along with altered localization of this normally mitochondria-localized protein [28,29]. Similarly to HSP60 expression, the presence of an autoimmune response directed to HSP60 is associated with a protective rather than a pathogenic effect in both adjuvant and human arthritis [30,31,32]. …”