Autoimmune intestinal pathology induced by hsp60-specific CD8 T cells.
Due to their ubiquitous distribution and high degree of structural similarity, heat shock proteins (hsp) are potential target antigens in autoimmune diseases. Here, we describe induction of intestinal inflammation following transfer of hsp60-reactive CD8 T cells into mice. Inflammatory reactions were MHC class I dependent and developed primarily in the small intestine. IFN gamma and TNF alpha, as well as gut-derived hsp60, were elevated at sites of T cell infiltration. Intestinal lesions were drastically reduced in mice lacking receptors for TNF alpha. Pathology also developed in germ-free mice, indicating recognition of host-derived hsp60 by CD8 T cells. This report demonstrates that CD8 T cells with defined antigen specificity cause intestinal inflammation, emphasizing a link between infection and autoimmune disease.
Steinhoff
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U
Department of Immunology, Max-Planck Institute of Infection Biology, Germany. steinhoff@mpiib-berlin.mpg.de
Brinkmann
V
V
Klemm
U
U
Aichele
P
P
Seiler
P
P
Brandt
U
U
Bland
P W
PW
Prinz
I
I
Zügel
U
U
Kaufmann
S H
SH
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018834:Chaperonin 60 / Q000276:immunology*; D003429:Cross Reactions; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D018834:Chaperonin 60; D015395:Histocompatibility Antigens Class I; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma