The Journal of Immunology, Vol 159, Issue 8 3692-3697, Copyright © 1997 by American Association of Immunologists

ARTICLES

CD4+ Th2 cells specific for mycobacterial 65-kilodalton heat shock protein protect against pristane-induced arthritis

JT Beech, LK Siew, M Ghoraishian, LM Stasiuk, CJ Elson and SJ Thompson
Department of Pathology and Microbiology, University of Bristol, United Kingdom.

Previous studies showed that mice with pristane-induced arthritis (PIA) and those protected from the disease by preimmunization with mycobacterial 65-kDa heat shock protein (hsp65), possess raised immune responses to hsp65. Thus, a paradox exists whereby T cells from both arthritic and hsp65-protected animals proliferate vigorously in response to the same Ag. Here we demonstrate that T cells from mice with PIA and hsp65-protected mice produce different cytokines in vitro in response to hsp65. The use of a sensitive CelELISA to measure Ag- driven lymphokine production revealed that spleen cells from hsp65- protected mice, but not those from pristane-injected or normal mice, produced the Th2-associated cytokines IL-4, IL-5, and IL-10 in response to stimulation with hsp65. By contrast, the Th1-associated cytokines IL- 2 and IFN-gamma were produced by spleen cells from mice of all groups in response to hsp65. Furthermore, there was a dramatic increase in the IgG1 to IgG2a ratio of anti-hsp65 Abs from arthritic to protected mice. Thus, it appears that a Th2 response is protective against PIA. To examine this theory, a regimen of IL-12 administration which polarizes the hsp65-specific (Th2) immune response toward Th1 was identified. This regime abolished hsp65-mediated protection against PIA. Other experiments revealed that the specificity of the response to hsp65 was important, as other bacterial proteins known not to protect against PIA induced similar Th2-associated cytokines in vitro. It is considered that the protection afforded by hsp65 preimmunization is mediated by Th2-associated cytokines produced by hsp65-specific CD4+ T cells.

This article has been cited by other articles:

				Md. Y. Mia, M. Durai, H. R. Kim, and K. D. Moudgil Heat Shock Protein 65-Reactive T Cells Are Involved in the Pathogenesis of Non-Antigenic Dimethyl Dioctadecyl Ammonium Bromide-Induced Arthritis J. Immunol., July 1, 2005; 175(1): 219 - 227. [Abstract] [Full Text] [PDF]

				M. S. Lillicrap, R. C. Duggleby, J. C. Goodall, and J. S. H. Gaston T cell recognition of a highly conserved epitope in heat shock protein 60: self-tolerance maintained by TCR distinguishing between asparagine and aspartic acid Int. Immunol., March 1, 2004; 16(3): 405 - 414. [Abstract] [Full Text] [PDF]

				B. J. Prakken, U. Wendling, R. van der Zee, V. P. M. G. Rutten, W. Kuis, and W. van Eden Induction of IL-10 and Inhibition of Experimental Arthritis Are Specific Features of Microbial Heat Shock Proteins That Are Absent for Other Evolutionarily Conserved Immunodominant Proteins J. Immunol., October 15, 2001; 167(8): 4147 - 4153. [Abstract] [Full Text] [PDF]

				A. G. A. Paul, P. J. S. van Kooten, W. van Eden, and R. van der Zee Highly Autoproliferative T Cells Specific for 60-kDa Heat Shock Protein Produce IL-4/IL-10 and IFN-{gamma} and Are Protective in Adjuvant Arthritis J. Immunol., December 15, 2000; 165(12): 7270 - 7277. [Abstract] [Full Text] [PDF]

				A. K. De, K. M. Kodys, B. S. Yeh, and C. Miller-Graziano Exaggerated Human Monocyte IL-10 Concomitant to Minimal TNF-{alpha} Induction by Heat-Shock Protein 27 (Hsp27) Suggests Hsp27 Is Primarily an Antiinflammatory Stimulus J. Immunol., October 1, 2000; 165(7): 3951 - 3958. [Abstract] [Full Text] [PDF]

				U. Wendling, L. Paul, R. van der Zee, B. Prakken, M. Singh, and W. van Eden A Conserved Mycobacterial Heat Shock Protein (hsp) 70 Sequence Prevents Adjuvant Arthritis upon Nasal Administration and Induces IL-10-Producing T Cells That Cross-React with the Mammalian Self-hsp70 Homologue J. Immunol., March 1, 2000; 164(5): 2711 - 2717. [Abstract] [Full Text] [PDF]

				S. Tanaka, Y. Kimura, A. Mitani, G. Yamamoto, H. Nishimura, R. Spallek, M. Singh, T. Noguchi, and Y. Yoshikai Activation of T Cells Recognizing an Epitope of Heat-Shock Protein 70 Can Protect Against Rat Adjuvant Arthritis J. Immunol., November 15, 1999; 163(10): 5560 - 5565. [Abstract] [Full Text] [PDF]

				S. J. Thompson, J. N. Francis, L. K. Siew, G. R. Webb, P. J. Jenner, M. J. Colston, and C. J. Elson An Immunodominant Epitope from Mycobacterial 65-kDa Heat Shock Protein Protects Against Pristane-Induced Arthritis J. Immunol., May 1, 1998; 160(9): 4628 - 4634. [Abstract] [Full Text] [PDF]