Regulation of lymphoid homeostasis by IL-2 receptor signals in vivo

High-affinity IL-2R signals are required for peripheral lpmphoid homeostasi s in vivo. We found that CD25 was required for regulation of peripheral T c ells in mice bearing either the DO11.10 MHC class II-restricted TCR transge ne or an Ia beta-null mutation, suggesting that MHC class I- and class II-d ependent T cell subsets are regulated independently by IL-2R signals. In co ntrast, deregulation of serum IgG1 levels in CD25(-/-) mice was dependent o n CD4(+) T cells. T cell expansion in DO11.10 CD25(-/-) mice was not prefer ential for cells escaping allelic exclusion by the TCR transgene, but was s uppressed by a Rag-2-null mutation. Together, these findings suggest that e ndogenous TCR are required to trigger T cell expansion, but that CD25 regul ates T cells activated by low-specificity signals. Expansion of DO11.10 T c ells in response to cognate Ag was modestly reduced in CD25(-/-) T cells tr ansferred into the normal lymphoid compartments of BALB/c mice. Moreover, a ctivation-induced clonal contraction and apoptosis in vivo were intact in t he absence of CD25, These data indicate that the regulatory role of high-af finity IL-2R signals extends beyond the control of Ag-specific responses an d suggest a role for these signals in control of bystander T cell activatio n.