Activation of T cells recognizing an epitope of heat-shock protein 70 can protect against rat adjuvant arthritis.
We have previously reported that CD4+ T cells recognizing a peptide comprising residues 234-252 of the heat shock protein (HSP)70 of Mycobacterium tuberculosis (M.tb) in the context of RT1.B MHC class II molecule emerged in the peritoneal cavity during the course of Listeria monocytogenes infection in rats and suppressed the inflammatory responses against listerial infection via IL-10 production. We report in this work that pretreatment with peptide 234-252 of HSP70 derived from M.tb suppressed the development of adjuvant arthritis (AA) in Lewis rats induced using heat-killed M.tb. T cells from rats pretreated with peptide 234-252 produced a significant amount of IL-10 in response to the epitope. T cells from rats pretreated with the peptide and immunized with M.tb produced the larger amount of IL-10 in response to the peptide, but only a marginal level of IFN-gamma in response to purified protein derivative of M.tb. Administration of anti-IL-10 Ab partly inhibited the suppressive effect of pretreatment with peptide 234-252 on the development of AA. Furthermore, transfer of a T cell line specific for the epitope at the time of AA induction markedly suppressed AA. These findings suggested that T cells recognizing peptide 234-252 may play a regulatory role in inflammation during AA via the production of suppressive cytokines including IL-10.
Tanaka
S
S
Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Japan.
Kimura
Y
Y
Mitani
A
A
Yamamoto
G
G
Nishimura
H
H
Spallek
R
R
Singh
M
M
Noguchi
T
T
Yoshikai
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism*; D007106:Immune Sera / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000276:immunology; D008055:Lipids; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008297:Male; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D018984:Epitopes, T-Lymphocyte; D018840:HSP70 Heat-Shock Proteins; D007106:Immune Sera; D008055:Lipids; D010446:Peptide Fragments; C114843:incomplete Freund's adjuvant; D016753:Interleukin-10; D005620:Freund's Adjuvant