CD4+ Th2 cells specific for mycobacterial 65-kilodalton heat shock protein protect against pristane-induced arthritis.
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.
Beech
J T
JT
Department of Pathology and Microbiology, University of Bristol, United Kingdom.
Siew
L K
LK
Ghoraishian
M
M
Stasiuk
L M
LM
Elson
C J
CJ
Thompson
S J
SJ
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D001426:Bacterial Proteins / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology; D018833:Chaperonins / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000097:blood; D007132:Immunoglobulin Isotypes / Q000097:blood; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009161:Mycobacterium / Q000276:immunology*; D013729:Terpenes; D018418:Th2 Cells / Q000276:immunology*
D001426:Bacterial Proteins; D018834:Chaperonin 60; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D018840:HSP70 Heat-Shock Proteins; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D013729:Terpenes; C074119:heat-shock protein 65, Mycobacterium; D018664:Interleukin-12; C009042:pristane; D018833:Chaperonins