Regulation of Lymphoid Homeostasis by IL-2 Receptor Signals In Vivo

• Published in: The Journal of immunology (1950) Vol. 164; no. 7; pp. 3527 - 3534
• Main Authors: Leung, Danny T. M, Morefield, Samantha, Willerford, Dennis M
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-04-2000
• Subjects: Alleles; Animals; CD25 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Homeostasis - genetics; Homeostasis - immunology; Interleukin 2 receptors; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; Lymphoid Tissue - cytology; Lymphoid Tissue - immunology; Lymphoid Tissue - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Transgenic; Ovalbumin - immunology; Peptide Fragments - immunology; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Receptors, Interleukin-2 - genetics; Receptors, Interleukin-2 - physiology; Signal Transduction - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.7.3527

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.