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. 2023 Jul 11;14:1204231. doi: 10.3389/fimmu.2023.1204231

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Copyright © 2023 Fazeli, Kalani and Hosseini

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The possible mechanism of T_SCM cell generation in T1D. An activated T cell undergoes mitosis coincidentally in the immune synapse forming between DC and naive T cells. After polarization, one of which becomes a fully activated daughter cell (because of permanent interaction with DC and receiving stimulatory signals) differentiating into CD25^hi CD127^low effector T cells. Another daughter cell (resting cell) without receiving a full-activation signal expressing CD25^low CD127^hi (T_SCM cell) migrates via chemokine receptor CXCR-4 upregulation linking to CXCL-12 into the bone marrow (BM). IL-7 in BM assists T_SCM cells in self-renewal by reducing their turnover. Once a second Ag stimulation occurs, T1D T_SCM cells that arrested in BM can reconstitute specific effector and memory autoreactive T cells.