SAT0204 NaÏve and recent thymic emigrant cd4+ t cells increase in rheumatoid patients treated with abatacept.
Authors: S. Piantoni, F. Regola, A. Tincani, P. Airò
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> CD4+ T cells in rheumatoid arthritis (RA) display a peculiar restriction of the T-cell receptor (TCR) repertoire which compromises their ability to react to novel antigens (1). We demonstrated that this process could be partially reverted by abatacept (ABA), which is a blocker of T lymphocyte co-stimulation, used in the treatment of RA (2). This effect could be at least in part due to a reduced generation of oligoclonal effector T cells, such as CD4+CD28-T cells (2). To better understand the mechanisms underlying this phenomenon, we speculated that ABA could influence the frequency of other peripheral T cell subpopulations, even at early stages of maturation. The homeostasis of the naïve T cell pool is maintained not only by thymus production, but also by mechanisms of peripheral replication involving TCR activation, which can be revealed by CD31 (PECAM-1) down-modulation (3). Indeed, CD4+CD45RA+CD31+ T cells have been described as recent thymic emigrants (RTE) newly produced by the thymus and CD4+CD45RA+CD31- T cells as central naïve, involved in a self-renewal peripheral process. This latter population may have a restriction of TCR repertoire and was shown to be involved in mechanisms of cardiovascular damage in patients with coronary syndrome (4). <h3>Objectives:</h3> We aimed at profiling circulating naïve CD4+CD45RA+ T cells, by assessing their expression of CD31. <h3>Methods:</h3> Thirty-one RA patients (median age [10°-90° percentile] 42 [25–64] years) were evaluated before and after 6 months of ABA therapy. The response to treatment was evaluated with the EULAR criteria. Phenotypic analysis of peripheral blood T lymphocytes was made by flow-cytometry. <h3>Results:</h3> After ABA therapy, the absolute number of total T CD4+ increased from 780 [423–1351] to 1000 [658–1566] cells/mm3 (p=0.01). Total naïve CD4+ increased in percentage (33 [18–56] vs 40 [20–61] % of CD4+; p=0.02) and in absolute number (257 [82–568] vs 344 [62–689] cells/mm3; p=0.03). In parallel, the number of RTE increased in percentage (10.6 [2–26] vs 11.6 [3–25] % of CD4+; p=0.04) and in absolute number (51 [15–194] vs 110 [23–271] cells/mm3; p=0.01). The central naïve counterpart did not show significant variations in percentage (29 [23–40] vs 27 [20–38] % of CD4+; p=0.20) nor in absolute number (191 [41–404] vs 242 [76–526] cells/mm3; p=0.20). The modifications of T cell number were not significantly different when good and moderate responder (n=22) and no responder (n=9) patients were compared, at baseline and after therapy. No correlation was found between age of patients, clinical features of the disease and RTE number at baseline and after 6 months. <h3>Conclusions:</h3> The number of total naïve T cells increases after therapy with ABA together with the number of RTE, suggesting a thymic output boost. Besides the peripheral effect in reducing the number of effector T cells which was showed by previous studies (5), ABA could have a role in promoting the immune reconstitution at the early stage of T cell development. Furthermore, a consequent favorable effect on possible cardiovascular damage mechanisms mediated by CD31- T cells might be hypothesized. <h3>References</h3> [1] Wagner UG, et al. PNAS1998. [2] Imberti L, et al. J Transl Med2015. [3] Kohler S, et al. Blood2009. [4] Flego D, et al. Basic Res Cardiol2014;109:448. [5] Airò P, et al. Trends Mol Med2013. <h3>Acknowledgements:</h3> Bristol-Myers-Squibb Italy provided an unrestricted research grant. <h3>Disclosure of Interest:</h3> None declared