Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen.
Transfer of naive antigen-specific CD4(+) T cells into lymphopenic mice that express an endogenous antigen as a systemic, secreted protein results in severe autoimmunity resembling graft-versus-host disease. T cells that respond to this endogenous antigen develop into effector cells that cause the disease. Recovery from this disease is associated with the subsequent generation of FoxP3(+)CD25(+) regulatory cells in the periphery. Both pathogenic effector cells and protective regulatory cells develop from the same antigen-specific T cell population after activation, and their generation may occur in parallel or sequentially. Interleukin (IL)-2 plays a dual role in this systemic T cell reaction. In the absence of IL-2, the acute disease is mild because of reduced T cell effector function, but a chronic and progressive disease develops late and is associated with a failure to generate FoxP3(+) regulatory T (T reg) cells in the periphery. Thus, a peripheral T cell reaction to a systemic antigen goes through a phase of effector cell-mediated pathology followed by T reg cell-mediated recovery, and both require the growth factor IL-2.
Knoechel
Birgit
B
Department of Pathology, University of California, San Francisco, School of Medicine, CA 94143, USA.
Lohr
Jens
J
Kahn
Estelle
E
Bluestone
Jeffrey A
JA
Abbas
Abul K
AK
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D018920:Coculture Techniques; D007111:Immunity, Cellular / Q000276:immunology; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2