Fig. 1.

A Stratification of T1D patients based on immunological profiles. Edner et al. used comprehensive immunological profiling to stratify T1D patients into responders (blue) and non-responders (red). Blood samples of T1D patients treated with CTLA4-Ig (abatacept) were analyzed through a machine learning approach that identified immunological profiles (high ICOS⁺T_FH, high CXCR5⁺ naive T cells), helping to stratify treated T1D patients into responders and non-responders. Responders were characterized by a reduction in T_FH (T follicular helper), Tph (T peripheral helper), ICOS⁺PD-1⁺T_FH, ICOS⁺PD-1⁻ T_FH, T regulatory, and ICOS⁺ memory and naive cells. B Possible mechanism of action for CTLA-4Ig (abatacept). Deactivation and dedifferentiation of TFH cells may be related to two mechanisms. 1. CTLA-4Ig inhibits crosstalk between the costimulatory molecules CD28 and CD80/CD86, altering T_FH cell differentiation at two “decision” points in the germinal centers of secondary lymphoid organs and the T-cell zone. 2. CTLA-4Ig interferes with CD28–CD80/86-mediated activation of CD4 T cells by DCs at the T-cell zone or CD4 T-cell interactions with B cells at the T:B cell border, consequently preventing T_FH cell differentiation, ICOS upregulation, and entry into B cell follicles. Once in the B cell follicle and the germinal center, abatacept neutralizes CD28–CD80/CD86 interaction among T_FH cells, GC B cells and follicular DCs (FDCs), further weakening T_FH cell differentiation and proliferation