Peptide antigen-induced T cell anergy limits clonal expansion but not Th1 effector function in vivo

T cell receptor transgenic T cells that recognize the chicken ovalbumin peptide 323-339 (OVAp) in the context of I-A^d were used to study the effects of peptide-induced tolerance on thymus-dependent immune responses in vivo. Adoptive transfer of transgenic T cells into nu/nu mice followed by aqueous intraperitoneal injection of OVAp resulted in T-cell anergy in both naive and antigen-experienced T cells, as measured by decreased proliferation and IL-2 production upon antigen rechallenge in vitro. When transferred into syngeneic BALB/c mice, these anergic T cells showed a defect in the ability to accumulate intracellular IL-2 and to clonally expand in vivo. Nevertheless, subcutaneous exposure of the transferred mice to OVAp in Complete Freund's Adjuvant permitted the differentiation of these anergic T cells into Th1-like helper cells, capable of secreting IFN-γ and participating in T-dependent IgG2a antibody responses and delayed-type hypersensitivity responses. Therefore, these data suggest that T-cell anergy induced by soluble peptide antigen limits the size of a T cell response by interfering with clonal expansion, but it does not necessarily regulate Th1-like effector function.