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Background: Most functions of tetraspanins are not related to cell-surface receptor ligand binding, but are mediated by direct interactions with their partner proteins. Functions of trimeric FcϵRI, expressed by antigen-presenting cells (APCs), range from amplification of allergic inflammatory reactions to their active suppression. Cell-type-specific protein-protein interactions might play a role in the regulation of these bidirectional tasks. Therefore, we intended to study the interactions of trimeric FceRI with tetraspanins. Methods: The expression levels of tetraspanins CD9, CD37, CD53, CD63, CD81, CD82, and CD151 on skin dendritic cells of atopic dermatitis (AD) patients or healthy individuals were detected by flow cytometry. Tetraspanin expression on FcϵRIpos and FcϵRIneg monocyte subpopulations was evaluated. Flow cytometry, confocal microscopy, immunoprecipitation, and immunoblotting experiments were performed to observe the relationship between tetraspanins CD9 and CD81 and FcϵRI. Furthermore, plate stimulation experiments were performed, and cytokines in the supernatants were detected. Results: We found that human FϵRIpos APCs expressed high amounts of tetraspanins and that the tetraspanins CD9 and CD81 were associated with FcϵRI. Concomitant activation of FcϵRI and CD9 on human monocytes increased FceRImediated cytokine release. Conclusion: Taken together, we show for the first time that CD9 and CD81 act as molecular partners of trimeric FϵRI on human APC, which might be of importance in allergic diseases such as AD. [ABSTRACT FROM AUTHOR]

To determine whether N K cells are involved in the regulation of the antibody response, we studied the effects of human NK clones on B-cell growth and differentiation and the mechanisms involved. We demonstrate that various human NK clones enhance the immunoglobulin production of SAC/rlL-2-activated B cells, e.g. IgG and IgM by up to 23% and anti-tetanus toxoid antibodies by up to430%.Cell cell interactions via cell-surface structures. e.g. the CD11a/ CDI8 molecule, were found lo be critical. Subsequently the NK-mediated B-cell regulation involves cytokines, since cell-free supernatants obtained by 48-h cultures of NK clones exerted BCGF and BCDF activity. Neutralization studies and direct determination characterized these cytokines as IFN-γ and TNF-α. The cytokine production of NK clones could be triggered by activated B cells only. Northern blot analysis demonstrated that activated B cells in co-culture with NK clones were able to induce accumulation of mRNA transcripts for IFN-γ and TNF-α in NK cells. [ABSTRACT FROM AUTHOR]

The role of natural killer (NK) cells in rheumatoid arthritis (RA) remains unclear. A pathogenetic function of rheumatoid factors (RF) also has not been defined. In the present studies, natural killer (NK) cells were examined as a model for FC gamma receptor type III-positive (FC gamma RIII+) cells, with regard to their interaction with RF. NK cell antigen CD16 (FC gamma RIII) and CD56 expression and functional NK and antibody-dependent cell-mediated cytotoxicity (ADCC) activity were compared in peripheral blood lymphocytes and autologous synovial fluid lymphocytes (SFL) of RA patients. Peripheral blood lymphocytes and SFL showed normal CD56 expression. In contrast, both the frequency and the density of CD16 antigen were decreased in SFL. Furthermore, diminished NK cytotoxicity and a significant decrease in ADCC were observed in SF NK cells. In subsequent in vitro studies with normal fresh NK cells, it was demonstrated that IgG-containing RF complexes from RA patients induced a modulation of FC gamma RIII structure from the NK cell surface, a decrease in NK activity, and a complete loss of ADCC. When purified RF was incubated with NK-enriched cell lines from RA patients, increased transcription and subsequent production of interferon-gamma and tumor necrosis factor alpha were observed. These data suggest a direct involvement of RF complexes in the pathogenetic process of chronic inflammation in RA.