Nonetheless, the NOD mouse can be induced to develop autoimmunity towards a number of target tissues other than the islets of Langerhans. While the selective loss of islet beta cells is well characterized, this murine strain is also highly susceptible to the induction of a panoply of autoimmune syndromes. Notably, the NOD mouse can develop hemolytic anemia, thyroiditis, encephalomyelitis, sialitis, and a lupus-like disorder. This pattern of disease susceptibility suggests the existence of overlapping immunologic perturbations among the NOD and other murine models of autoimmunity. Determining the mechanistic underpinning of these findings may further our understanding of common derangements that predispose to autoimmunity. Among regulatory elements of immune effector functions, the CD4 T lymphocyte compartment plays a predominant role in the initiation of the immune response. Since autoimmune diseases manifest diverse pathogenic mechanisms, a perturbation in immune regulation by CD4 T lymphocytes may be a common phenotype driving these disorders. In this regard, it has been amply demonstrated that the appropriate differentiation of CD4 T cells toward regulatory/effector mechanisms is intimately linked to a precise pattern of proliferation. A proscribed number of cell divisions is required for CD4 T cells to acquire the capacity to secrete particular cytokine profiles and to undergo activation induced cell death, a paramount mechanism in protection from autoimmunity. We have previously Nardosinone reported that CD4 T lymphocytes in the NOD mouse exhibit an aberrant division profile highlighted by their inability to achieve advanced numbers of divisions following polyclonal activation, a finding in agreement with several other published observations. As the NOD mouse demonstrates susceptibility to a lupus-like Epiberberine syndrome, we investigated whether the aberrancy in the activation profile of CD4 T lymphocytes might be shared with murine models of spontaneous lupus.For this purpose, we utilized the wellcharacterized spontaneous murine models of this disease, the MRL and the NZBxNZW F1 strains, to ascertain the characteristics of CD4 T cell activation.