Costimulatory activity of human synovial fibroblasts.

UNLABELLED: T cell activation initiated via the CD3/TCR complex requires signals provided by the interaction between costimulatory receptors on T cells and their corresponding ligands on accessory cells. Human dermal fibroblasts are reported to be deficient in this costimulatory activity and normally cannot serve as accessory cells for activation of resting T cells. We examined the contribution of human synovial fibroblasts to costimulatory activity for resting T cells. METHODS: Synovial fibroblast, dermal fibroblast, and umbilical cord endothelial cell cultures were established. These cell lines were co-cultured with purified peripheral T cells; and T cell activation was assayed using 3H-thymidine. RESULTS: Culturing resting T cells with synovial fibroblasts resulted in T cell proliferation with either mitogenic (periodate) or alloantigenic stimulation. This activation was dependent on the addition of interleukin 1 and/or gamma interferon. CONCLUSION: In contrast to dermal fibroblasts, synovial fibroblasts are able to provide costimulatory activity for activation of resting T cells.

Accumulation of interferon gamma-producing TH1 helper T cells in nasal polyps.

We investigated the mechanisms involved in the formation of nasal polyps by examining T-cell clones and their production of soluble mediators in nasal polyps. Recently, the allergic origin of nasal polyps has been challenged. To study this question we characterized T cells from polyp tissue of allergic individuals in terms of their cytokine pattern. Nasal polyp T cells were cloned from allergic individuals undergoing polypectomy. Polyp tissue was dispersed enzymatically, and T cells were stimulated with mitogen and interleukin-2. Control T cells were obtained from peripheral blood of nonallergic donors. Cytokine production of interleukin-4 and interferon was then determined by indirect enzyme-linked immunosorbent assay tests. Polyp T-cell clones were found to produce high interferon but low interleukin-4 levels that were not significantly different from control peripheral blood T-cell clones. In addition, immunoglobulin production by dispersed polyp tissue was investigated. Immunoglobulin levels were higher in polyp tissues than in serum with immunoglobulin A predominating. These results suggest that the inflammatory reaction in nasal polyps is different than that seen in a typical type I hypersensitivity response.

Protein tyrosine phosphorylation triggered by human Fc gamma RII.

The role of the cytoplasmic domain of human Fc gamma RII in cellular activation was studied by transfecting P815 cells with different isoforms or deletion mutants of this receptor and then assaying protein tyrosine phosphorylation after crosslinking with anti-CD32 monoclonal antibodies. Fc gamma RIIa, but not Fc gamma RIIb1 or b2, was able to trigger tyrosine phosphorylation. Deletion of just the carboxyl-terminal 19 amino acids of Fc gamma RIIa markedly reduced induction of protein tyrosine phosphorylation. Deletion of the carboxyl-terminal 38 amino acids of the cytoplasmic domain completely eliminated this response. These results indicate the cytoplasmic domain of human Fc gamma RIIa, the form of Fc gamma RII that predominates on human myeloid cells and platelets, contains sequences that allow activation of tyrosine phosphorylation; Fc gamma RIIb isoforms, the form of Fc gamma RII on human B lymphocytes, lack these sequences.

Cytokine production by mite-specific T cells from donors with mild atopic disease.

This study was designed to determine whether allergen-specific T cells from patients with mild atopic disease were similar to TH2 cells. Tetanus-specific and house mite-specific T-cell clones were derived from peripheral blood of donors with strong immediate epicutaneous skin tests to Dermatophagoides farinae but with mild allergic disease. Overall, the tetanus- and mite-specific clones produced similar amounts of interleukin-4 (IL-4) and gamma interferon (INF-gamma). However, when donors were divided into those with high and low serum levels of mite-specific IgE as determined by RAST, mite-specific clones from donors with high specific IgE produced significantly more IL-4 and less IFN-gamma than mite-specific clones from donors with low levels of specific IgE. These results suggest that circulating allergen-specific T cells from patients who do not have severe allergic disease may nonetheless be skewed toward a TH2 profile. We also examined IL-4 and IFN-gamma production during primary culture of antigen-stimulated peripheral blood mononuclear cells. Detectable amounts of IL-4 were not produced. Stimulation with tetanus antigen induced two to three times as much IFN-gamma as did stimulation with mite antigen. However, the amount of IFN-gamma produced during primary culture did not correlate with the cytokine production of the T-cell clones subsequently generated.