Table 2 Endpoints of the study

Primary Endpoints

• T cell subsets:

- CD4 and CD8 positive T cells: naïve T cells, T effector cells, T memory cells, regulatory T cells

- T-helper subsets: Th1, Th2, Th17

• B cell subsets:

- Recent bone marrow emigrants, mature naïve, memory B cells

- Plasma cells

• Natural killer cells:

- CD56bright, CD56dim

- Natural killer T cells

• Antigen-presenting cells:

- Dendritic cells: CD303⁺ plasmacytoid, CD11c⁺ and CD141⁺ myeloid dendritic cells

- Monocytes and macrophages

• Myeloid-derived suppressor cells

• Markers of autoimmunity in the serum (every 6 months):

- ANA, cANCA, pANCA, anti-dsDNA, anti-TSHR, anti-TPO, RF, anti-CCP, anti-GBM, anti-platelet antibodies

Secondary Endpoints

• Activation status of cell surface receptors assessed by flow cytometry:

- Relative and absolute change from baseline of mean fluorescence intensity (MFI) and the proportion of positive cells regarding CD25, HLA-DR, LFA-1, CD29, CD69, CD71 expression

• Expression of co-inhibitory molecules assessed by flow cytometry:

- Relative and absolute change from baseline of MFI and of the proportion of positive cells regarding PD-1 = CD279, ICOS = CD278, TIM-3, CTLA4 expression

• Effector functions of CD4 and CD8 positive T cells:

- Relative and absolute change from baseline of the results of cell proliferation assays assessed as the percentage of proliferated cells

- Relative and absolute change from baseline of cytokine production measurement assessed as concentration

- Relative and absolute change from baseline of the cytolytic activity assessed by flow cytometry measurement of MFI and proportion of positive cells regarding Granzyme B, Perforin and CD107a expression

- Relative and absolute change from baseline of intracellular calcium response assessed as a ratio

• Migrational capacity:

- Relative and absolute change from baseline MFI and the proportion of positive cells assessed by flow cytometry expression analysis of CD11a, CD31, CD44, CD49d, CCR5, CCR6, CCR7

- Absolute and relative change of cell numbers of migrated cells compared to baseline assessed in an in vitro model by flow cytometry analysis

• High-throughput TCR- and BCR sequencing of the T- and B cell rep-ertoire concerning the expansion of distinct clones:

- Qualitative comparison of the distribution of CDR3 sequences

• Regulatory T-cell function:

- Relative and absolute change from baseline in production of TGF-beta and IL-10 of CD4⁺CD25⁺FOXP3⁺ regulatory T cells

- Suppression of T cell proliferation: Relative and absolute change from baseline in responder T cell proliferation assessed by suppression assays