Breakdown of peripheral T-cell tolerance by chronic interleukin-15 elevation.
Thymic deletion purges the repertoire of most developing T cells with the potential for overt self-reactivity, but some self-specific cells do emerge into the peripheral pool. Under most conditions, these potentially autoaggressive cells remain in a quiescent state. However, in some circumstances, they become activated and acquire effector function, leading to immune disease. It is thus important to clarify the mechanism(s) responsible for determining the balance between such inappropriate T-cell activation and the normal state of peripheral tolerance. In this article, we show that chronic elevation of interleukin-15 levels interferes with the tolerant state of CD8+ T cells through a process that involves activation of nonlymphoid antigen-presenting cells by CD4+asialo-GM1+ (ASGM1) or both CD4+ASGM1- and CD4-ASGM1+ cells. These findings suggest a potential role for dysregulated interleukin-15 production in promoting tolerance breakdown. This new information may be of potential use in improving tumor vaccines to self-antigens and in ameliorating autoimmune or graft-versus-host disease.
Maekawa
Yoichi
Y
Department of Immunology and Parasitology, School of Medicine, University of Tokushima, Tokushima, Japan.
Tsukumo
Shin-Ichi
S
Okada
Hiroko
H
Kishihara
Kenji
K
Yasutomo
Koji
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016332:Fetal Tissue Transplantation; D006086:Graft vs Host Disease / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D007108:Immune Tolerance / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism*; D008099:Liver / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008806:Mice, Inbred AKR; D016513:Mice, SCID; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology; D018183:Transplantation Chimera
D019409:Interleukin-15