Regulation of lymphoid homeostasis by IL-2 receptor signals in vivo.
High-affinity IL-2R signals are required for peripheral lymphoid homeostasis in vivo. We found that CD25 was required for regulation of peripheral T cells in mice bearing either the DO11.10 MHC class II-restricted TCR transgene or an Iabeta-null mutation, suggesting that MHC class I- and class II-dependent T cell subsets are regulated independently by IL-2R signals. In contrast, deregulation of serum IgG1 levels in CD25-/- mice was dependent on CD4+ T cells. T cell expansion in DO11.10 CD25-/- mice was not preferential for cells escaping allelic exclusion by the TCR transgene, but was suppressed by a Rag-2-null mutation. Together, these findings suggest that endogenous TCR are required to trigger T cell expansion, but that CD25 regulates T cells activated by low-specificity signals. Expansion of DO11.10 T cells in response to cognate Ag was modestly reduced in CD25-/- T cells transferred into the normal lymphoid compartments of BALB/c mice. Moreover, activation-induced clonal contraction and apoptosis in vivo were intact in the absence of CD25. These data indicate that the regulatory role of high-affinity IL-2R signals extends beyond the control of Ag-specific responses and suggest a role for these signals in control of bystander T cell activation.
Leung
D T
DT
Department of Medicine, University of Washington, School of Medicine, Seattle, WA 98195, USA.
Morefield
S
S
Willerford
D M
DM
D000483:Alleles; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
C111390:OVA 323-339; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D010047:Ovalbumin