Inflammation activates self hsp60-specific T cells.
Injection of incomplete Freund's adjuvant (IFA) into the footpads of BALB/c mice induced an acute inflammation. Draining popliteal lymph nodes showed major histocompatibility complex (MHC) class II-restricted proliferation when challenged in vitro with recombinant Mycobacterium bovis 65-kDa heat shock protein (hsp65). alpha beta T cell receptor-positive, CD4+, hsp65-specific T cell lines and clones were generated from these lymph nodes, and 87% of clones responded to a beta galactosidase fusion protein containing residues 238-573 of human hsp60. Seventy percent of these hsp60-responsive clones also responded to a synthetic peptide corresponding to residues 412-423 of the mouse hsp60. This peptide also induced significant responses in IFA-primed lymph node cells but not in lymphoid cells from unimmunized mice. These results demonstrate that T cells specific for epitopes in self hsp60 are activated during inflammatory responses induced in the absence of exogenous bacterial hsp65. The findings of this study may provide a basis for understanding the often reported isolation of mycobacterial hsp65-responsive T cells from inflammatory sites of arthritis patients, and the protective effects of preimmunization with hsp65 in experimental models of arthritis.
Anderton
S M
SM
Department of Medicine (Rheumatology), University of Newcastle upon Tyne, GB.
van der Zee
R
R
Goodacre
J A
JA
D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000032:analysis; D005620:Freund's Adjuvant / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007114:Immunization; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D006360:Heat-Shock Proteins; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D005620:Freund's Adjuvant