Showing papers by "Christine Ambrose published in 1999"

Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations.

Abstract: The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti–DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.

BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth.

Abstract: Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M-stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center-like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.

Signaling Through the Lymphotoxin-β Receptor Stimulates HIV-1 Replication Alone and in Cooperation with Soluble or Membrane-Bound TNF-α

Abstract: The level of ongoing HIV-1 replication within an individual is critical to HIV-1 pathogenesis Among host immune factors, the cytokine TNF-α has previously been shown to increase HIV-1 replication in various monocyte and T cell model systems Here, we demonstrate that signaling through the TNF receptor family member, the lymphotoxin-β (LT-β) receptor (LT-βR), also regulates HIV-1 replication Furthermore, HIV-1 replication is cooperatively stimulated when the distinct LT-βR and TNF receptor systems are simultaneously engaged by their specific ligands Moreover, in a physiological coculture cellular assay system, we show that membrane-bound TNF-α and LT-α 1 β 2 act virtually identically to their soluble forms in the regulation of HIV-1 replication Thus, cosignaling via the LT-β and TNF-α receptors is probably involved in the modulation of HIV-1 replication and the subsequent determination of HIV-1 viral burden in monocytes Intriguingly, surface expression of LT-α 1 β 2 is up-regulated on a T cell line acutely infected with HIV-1, suggesting a positive feedback loop between HIV-1 infection, LT-α 1 β 2 expression, and HIV-1 replication Given the critical role that LT-α 1 β 2 plays in lymphoid architecture, we speculate that LT-α 1 β 2 may be involved in HIV-associated abnormalities of the lymphoid organs