Cytokines in the induction and circumvention of peripheral tolerance.

Injection of deaggregated (monomeric) human gamma globulin (DHGG) into mice induces a state of immunological tolerance to subsequent challenge with immunogenic forms of HGG. Tolerance was shown to be induced in both the Th1 and Th2 CD4+ subsets. These mice fail to demonstrate antibody production, T cell proliferation, cytokine release, or T cell helper function.

Evidence for an underlying CD4 helper and CD8 T-cell defect in B-cell-deficient mice: failure to clear persistent virus infection after adoptive immunotherapy with virus-specific memory cells from muMT/muMT mice.

Adoptive transfer of virus-specific memory lymphocytes can be used to identify factors and mechanisms involved in the clearance of persistent virus infections. To analyze the role of B cells in clearing persistent infection with lymphocytic choriomeningitis virus (LCMV), we used B-cell-deficient muMT/muMT (B-/-) mice. B-/- mice controlled an acute LCMV infection with the same kinetics and efficiency as B-cell-competent (B+/+) mice via virus-specific, major histocompatibility complex (MHC) class I-restricted CD8(+) cytotoxic T lymphocytes (CTL).

CD4+ T-cell subsets and cytokines involved in peripheral tolerance.

Peripheral tolerance is induced under conditions that avoid activation of antigen-presenting cells (APCs) to release cytokines. Such tolerance occurs in both CD4+ T helper (Th)-cell subsets (Th1 and Th2), probably because it is induced in precursor cells. By contrast, activation of APCs to release cytokines by immunization or infection activates either both subsets or predominantly one of them.

CD40 ligand expressed on B cells in the BXSB mouse model of systemic lupus erythematosus.

Male BXSB mice, unlike female BXSB, develop a severe early onset lupus-like disease that has been linked to an intrinsic B cell defect. In investigating this B cell defect the present study showed that male, but not female, BXSB contained a higher percentage of large, activated splenic B cells that were more responsive to anti-CD40 mAb-induced proliferation. The hyperactivity of the large B cells from the male mice was also observed in the absence of anti-CD40 mAb or any other stimuli.