B cell tolerance to self-antigen is critical to preventing antibody-mediated autoimmunity. Previous work using B cell antigen receptor transgenic animals suggested that self-antigen-specific B cells are either deleted from the repertoire, enter a state of diminished function termed anergy, or are ignorant to the presence of self-antigen. These mechanisms… (More)
T cells activated by antigen receptor stimulation in the absence of accessory cell-derived costimulatory signals lose the capacity to synthesize the growth factor interleukin-2 (IL-2), a state called clonal anergy. An analysis of CD3- and CD28-induced signal transduction revealed reduced ERK and JNK enzyme activities in murine anergic T cells. The amounts… (More)
BACKGROUND Mutation of a tumor suppressor allele leaves the second as backup. Not necessarily so with p53. This homo-tetrameric transcription factor can become contaminated with mutant p53 through hetero-tetramerization. In addition, it can be out-competed by the binding to p53 DNA recognition motifs of transactivation-incompetent isoforms (DeltaN and… (More)
The role of apoptosis in affinity maturation was investigated by determining the affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific antibody-forming cells (AFCs) and serum antibody in transgenic mice that overexpress a suppressor of apoptosis, Bcl-xL, in the B cell compartment. Although transgenic animals briefly expressed higher numbers of splenic… (More)
The identification and characterization of a newly extended family of molecules related to the T-cell costimulatory proteins CD28 and B7 suggests that a distinct form of costimulatory signals could be important for effector T-cell responses outside of lymphoid tissues.
The role of anergy, an acquired state of T cell functional unresponsiveness, in natural peripheral tolerance remains unclear. In this study, we found that anergy was selectively induced in fetal antigen-specific maternal CD4(+) T cells during pregnancy. A naturally occurring subpopulation of anergic polyclonal CD4(+) T cells, enriched for self… (More)
A loss of T cell tolerance underlies the development of most autoimmune diseases. The design of therapeutic strategies to reinstitute immune tolerance, however, is hampered by uncertainty regarding the molecular mechanisms involved in the inactivation of potentially autoreactive T cells. Recently, E3 ubiquitin ligases have been shown to mediate the… (More)
An experimental study investigated the influence of priming on helping behavior. A scrambled sentence test was used to prime groups with the concepts of altruism or egoism. In a third group a neutral concept was activated. The results indicated that there is no difference in helping behavior between the altruism and the neutral group. However, in the egoism… (More)
The spontaneous development of destructive polyarthritis in mice transgenic for an autoreactive T-cell receptor supports the notion that a failure of T-cell self-tolerance can lead to similar diseases in humans, and sheds new light on the role of peripheral tolerance in the avoidance of such pathological immune responses.