CD4+ T cells pass through an effector phase during the process of in vivo tolerance induction.
An important process in the generation of tolerance to peripheral self-Ags is the induction of unresponsiveness in mature specific T cells. Although the end stage of this process, termed anergy, is well defined, the pathway by which naive T cells become anergic remains to be elucidated. Using an in vivo self-tolerance model, we demonstrate that CD4(+) T cells pass through a significant effector stage on their way to an anergic state. This stage is characterized by production of effector cytokines, provision of help for CD8(+) T cells, and induction of in vivo pathology within organs that express cognate Ag. These results suggest that the initial activation stage in T cell tolerance is similar to that seen in memory induction. They also suggest that autoimmune pathology can result during the natural process of tolerance induction rather than requiring that tolerance be broken.
Huang
Ching-Tai
CT
Oncology Center and Division of Comparative Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
Huso
David L
DL
Lu
Zhenbing
Z
Wang
Tianhong
T
Zhou
Gang
G
Kennedy
Eugene P
EP
Drake
Charles G
CG
Morgan
David J
DJ
Sherman
Linda A
LA
Higgins
Amy D
AD
Pardoll
Drew M
DM
Adler
Adam J
AJ
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics / Q000401:mortality / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000096:biosynthesis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D008171:Lung Diseases / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D018448:Models, Immunological; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D011948:Receptors, Antigen, T-Cell