Abrogation of CD30 and OX40 signals prevents autoimmune disease in FoxP3-deficient mice

FoxP3-deficient mice are rescued from tissue and organ destruction and subsequent lethal autoimmune disease by the combined absence of OX40 and CD30 signals

Treg and CTLA-4: Two intertwining pathways to immune tolerance.

Both the CTLA-4 pathway and regulatory T cells (Treg) are essential for the control of immune homeostasis. Their therapeutic relevance is highlighted by the increasing use of anti-CTLA-4 antibody in tumor therapy and the development of Treg cell transfer strategies for use in autoimmunity and transplantation settings. The CTLA-4 pathway first came to the attention of the immunological community in 1995 with the discovery that mice deficient in Ctla-4 suffered a fatal lymphoproliferative syndrome. Eight years later, mice lacking the critical Treg transcription factor Foxp3 were shown to exhibit a remarkably similar phenotype. Much of the debate since has centered on the question of whether Treg suppressive function requires CTLA-4. The finding that it does in some settings but not in others has provoked controversy and inevitable polarization of opinion. In this article, I suggest that CTLA-4 and Treg represent complementary and largely overlapping mechanisms of immune tolerance. I argue that Treg commonly use CTLA-4 to effect suppression, however CTLA-4 can also function in the non-Treg compartment while Treg can invoke CTLA-4-independent mechanisms of suppression. The notion that Foxp3 and CTLA-4 direct independent programs of immune regulation, which in practice overlap to a significant extent, will hopefully help move us towards a better appreciation of the underlying biology and therapeutic significance of these pathways

Local convergence for a family of third order methods in Banach spaces

We present a local convergence analysis of a family of third order methods for approximating a locally unique solution of nonlinear equations in a Banach space setting. Recently, the semilocal convergence analysis of this method was studied by Chun, Stanic ˘ a and Neta in [10]. ˘ These authors extended earlier results by Kou, Li [17] and others [8, ?, 11, 13, 14]. The convergence analysis is based on hypotheses up to the second Frechet derivative of the operator involved. This work further extends the ´ results of [10] and provides computable convergence ball and computable error bounds under hypotheses only up to the first Frechet derivative.&nbsp