Influence of donor variability on macrophage and dendritic cell mediated T cell activation during the phagocytosis of C1q-bound apoptotic cells
Mentor:Andrea Tenner, Professor of Molecular Biology and Biochemistry, University of California, Irvine
It is well established that in humans, deficiency of complement protein C1q results in the autoimmune disease Systemic Lupus Erythematosus (SLE). SLE can lead to organ failure and eventually death. One cause of SLE may be the inefficient clearance of apoptotic cells (AC). Macrophages (Mφ) ingesting AC with C1q bound to them ingest the AC and have enhanced production of anti-inflammatory and reduced production of inflammatory cytokines relative to AC without C1q. These changes suppress the production of autoantibodies which are a dominant cause in tissue damage that leads to clinical symptoms in SLE. Using a primary human cell autologous system, the influence of Mφ and dendritic cells (DC) ingesting C1q-bound late apoptotic lymphocytes (C1q-LAL) on T cell activation is being investigated. Here, whether human donor variability in Mφ and DC phenotype could affect the influence of C1q on T cell activation was determined. Thus, CD40, CD80 and CD86 expression levels of Mφ/DC were measured and compared to the Mφ/DC-mediated T cell responses in each experiment as these markers are co-stimulatory ligands for T cell activation which is assessed here by proliferation. Donor variability was observed, but all data were under 2 standard deviation from the mean (n=5). Thus far, the donor with the highest CD40 and CD80 expression had the highest overall CD4+ and CD8+ T cell proliferation for Mφ/DC only Mφ+LAL/DC+LAL, and Mφ+C1q-LAL/DC+C1q-LAL (n=3). Thus, donor variability in Mφ and DC phenotype correlates with overall T cell activation but does not alter the effect of C1q on T cell activation.