Page 6 - ISNI abstracts

International Joint Israel-Greek-Italian Neuroimmunological meeting hi Foxp3 CD45RA CD39 Treg cells in Multiple Sclerosis - + Gargano F.1, Sambucci M.1, De Bardi M.1, Gasperini C.2, Ruggieri S.2, De Rosa V.3, Matarese G.4, Borsellino G.1 and Battistini L.1 1 Neuroimmunology Unit, Santa Lucia Foundation, Rome, Italy. 2 Department of Neuroscience “Lancisi”, San Camillo Hospital, Rome, Italy. 3 Laboratory of Immunology, Institute of Endocrinology and Experimental Oncology, National Research Council (IEOS-CNR), Naples, Italy. 4 Department of Medicine and Surgery, University of Salerno, “Baronissi Campus” Salerno, Italy. FoxP3 is a key transcription factor for the development and function of natural CD4 regulatory + T cells (Treg cells). These cells play an indispensable role for the maintenance of self-tolerance and immune homeostasis. In particular, their role is crucial in autoimmune diseases such as Multiple Sclerosis, and also in allergies and cancer. In contrast to murine FoxP3 Treg cells, + human FoxP3 cells may not be functionally homogenous. Some Foxp3 cells, in fact, present + + + in peripheral blood of adults are phenotypically naïve (CD45RA ) and they are suppressive in vitro, whereas other Foxp3 cells phenotypically resemble memory T cells (CD45RA ) and - + are suggested to originate from peripheral memory Foxp3 CD4 T cells. Here we show that + - human Foxp3 CD4 T cells, finely discriminated based on expression of Foxp3 and cell surface + + phenotype, should be separated into three main different subpopulations: CD45RA Foxp3 , lo + lo - CD45RA Foxp3 , CD45RA Foxp3 . This analysis unveils different percentages of Treg hi - subpopulations in Multiple Sclerosis patients compared to healthy controls. Interestingly, these subpopulations can be further separated with the combination of CD39. The subpopulation that carries the highest in vitro suppressive activity (CD45RA Foxp3 ) expresses the highest - hi levels of CD25 and CD39, and their frequency is significantly reduced in MS patients compared - to healthy donors. We propose that CD45RA Foxp3 Treg are activated Treg cells, whereas hi CD45RA Foxp3 are resting Treg cells. The higher proportion in healthy donors of CD39+ cells lo + hi within CD45RA Foxp3 cells could indicate a higher fraction of potent immunosuppressive - cells compared to the lower CD39 percentages within CD45RA-Foxp3 cells in Multiple hi + Sclerosis patients. In conclusion, we propose the introduction of CD45RA and CD39 markers coupled to “classical” CD25 and Foxp3 expression to precisely identify functionally distinct Treg subsets. This will help understand immune responses in health and disease. 6