Naive CD4+ T cells from lupus-prone Fas-intact MRL mice display TCR-mediated hyperproliferation due to intrinsic threshold defects in activation.

Autoreactive T cell activation is a consistent feature of murine lupus; however, the mechanism of such activation remains unclear. We hypothesized that naive CD4+ T cells in lupus have a lower threshold of activation through their TCR-CD3 complex that renders them more susceptible to stimulation with self-Ags. To test this hypothesis, we compared proliferation, IL-2 production, and single cell calcium signaling of naive CD4+ T cells isolated from Fas-intact MRL/+(Fas-lpr) mice with H-2k-matched B10.

Oxazolone and diclofenac-induced popliteal lymph node assay reactions are attenuated in mice orally pretreated with the respective compound: potential role for the induction of regulatory mechanisms following enteric administration.

The murine popliteal lymph node assay (PLNA) was examined as a preclinical assay with the potential to identify low-molecular-weight compounds (LMWCs) that are likely to be associated with immune-mediated drug hypersensitivity reactions (IDHRs) in humans. We hypothesized that the contact sensitizer oxazolone (OX) would cause a strong PLN reaction in naive mice and that the PLN reaction would be attenuated in mice orally pretreated with OX due to the induction of oral tolerance. In naive mice, OX induced a strong PLN reaction and caused dose-dependent increases in PLN size, weight, cellularity, percentage of CD4(+) PLN T cells, and percentage of PLN B cells, with a concomitant decrease in the percentage of CD8(+) PLN T cells.

Intrinsic T cell defects in systemic autoimmunity.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of T cell tolerance to nuclear antigens. Studies in mice and humans have demonstrated that T cells from individuals with lupus are abnormal. Here, we review the known T cell defects in lupus and their possible biochemical nature, genetic causes, and significance for lupus pathogenesis.

CD4+ T cells from lupus-prone mice avoid antigen-specific tolerance induction in vivo.

Activated T cells in spontaneous lupus presumably bypass normal tolerance mechanisms in the periphery, since thymic tolerance appears intact. To determine whether such T cells indeed avoid in vivo peripheral tolerance mechanisms, we assessed their activation and recall responses after in vivo Ag stimulation in the absence of exogenously supplied costimulatory signals. Naive CD4(+) AND (transgenic mice bearing rearranged TCR specific for pigeon cytochrome c, peptides 88-104) TCR-transgenic T cells, specific for pigeon cytochrome c, from lupus-prone Fas-intact MRL/Mp+(Fas-lpr) and from H-2(k)-matched control CBA/CaJ and B10.

Chemotaxis-promoting and adhesion properties of human tonsillar follicular dendritic cell clusters.

Lymph follicles are globular and compact due to aggregation of lymphoid cells on follicular dendritic cells (FDC). To probe the mechanisms underlying this accumulation of cells, we analyse here the role played by FDCs in attracting and binding cells. FDCs prepared from human tonsils by mild separation techniques appeared in the form of clusters (FDC clusters), where, via cytoplasmic extensions, they enveloped lymphoid cells.