Immunobiology of antigen presenting cells during relapse vs. remission in multiple sclerosis

• Published in: The Journal of immunology (1950) Vol. 196; no. 1_Supplement; pp. 49 - 49.8
• Main Authors: Sinha, Sushmita, Cunnusamy, Khrishen, Chaudhary, Parul, Greenberg, Benjamin M, Frohman, Elliot M, Karandikar, Nitin J
• Format: Journal Article
• Language: English
• Published: 01-05-2016
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.196.Supp.49.8

Multiple sclerosis (MS) is the most common cause of neurological disability in young adults. Approximately 80% of MS patients initially present with the relapsing-remitting disease. Although studies suggest immune hyperactivity during relapse, role of specific immune cells has been understudied. We investigated whether APCs might be the drivers of inflammation during an MS-relapse. Paired blood samples were obtained from patients during relapse (Rel) and remission (Rem) phase of MS. APCs were immunophenotyped for activation, inhibition and migration-associated markers. T cell-cytokine stimulatory potential of Rel vs. Rem-APCs was studied by co-culturing sorted APC-subtypes with healthy donor-CD3+ T cells. Rel-monocytes displayed a significantly higher expression of adhesion molecules while inhibitory receptor ILT4 was significantly increased on Rem-monocytes. Further, Rel-monocytes stimulated significantly more IFN-g and IL-17 from allogeneic CD4+ T-cells. Rel- B-cells had a significantly higher expression of adhesion molecules and displayed significantly increased potential of stimulating IFN-g from allogeneic CD8+ T-cells. Inhibitory receptor ILT3 was significantly increased on PDCs during Rem. Functionally, Rel-MDC stimulated significantly more IL-17 and IFN-g from allogeneic CD4+ and CD8+ T-cells, respectively. Overall, our study suggests that these key differences in APC subsets during Rel vs Rem phases could potentially modulate T cell responses by favoring more pro-inflammatory T-cell phenotype during MS relapse. Combined with our publications related to differential regulatory ability of CD4 and CD8 T-cells this study provides great insights into the underlying immunopathology of an MS relapse.