T CELL SUBTYPES IN MANAGEMENT OF OSTEOPOROSIS WITH BISPHOSPHONATES AND THE AUTOIMMUNE REACTION TO THE COLLAGEN IN RHEUMATOID ARTHRITIS.

T lymphocytes with different T cell receptors are at the crossroad of inflammation and autoimmunity. We investigated the role of γδTCR and αβTCR T lymphocytes (γδT, αβT cells) in two model conditions represented by zoledronic acid (ZA)-induced acute phase reactions (APR) and in the immune reaction against collagen in rheumatoid arthritis (RA). First, γδTCR T lymphocytes (γδTcells) are specifically activated by ZA infusion in the treatment of osteoporosis and is frequently associated with the onset of APR, possibly via 25-OH vitamin D (25-OHvD) levels. 50% of patients reported ZA-associated APR (APR+). APR+ cases had a higher percentage of central memory Th1-like γδTcells before treatment. One week after ZA infusion, a decreased percentage of central memory Th1-like γδTcells, an increase in the percentage and activation of effector memory Th1-like γδTcells, and an increase in Th17-like γδTcells were observed in the patients with APR. Lower 25-OHvD levels were significantly associated to APR, but no correlation was found between 25-OHvD level and γδTcell percentage or subsets. Second, αβTCR T lymphocytes (αβTcells) in RA recognize the DR4/DR1-restricted epitope 261-273 of the human type II collagen, whereas B cells recognize the epitope 359-369. We investigated the role of B and T cell epitopes and their post-translational modifications on the RA adaptive immune response. PBMCs from 5 HLA-DR4+ monozygotic twins, two HLA-DR4+ and one HLA-DR3+ healthy donor and synovial fluids (SF) from an HLA-DR4+ RA patient and HLA-DR3+ patient were used and cells cultured with the native form of the collagen T epitope (261-273T), its K264 carbamylated form (homocit261-273T), the native form of the collagen B epitope (359-369B), its R360 citrullinated form (cit359-369B) or the combination of the native and modified epitopes. We may conclude that the collagen T epitope 261-273 has a role in the pathogenesis of RA, but the carbamilation of this epitope dos not seem to be influent in the T cell response.