APOL1 risk alleles modulate T cell receptor signaling to promote allograft rejection
John Pell, EM Tanvir, Zeguo Sun, Irene Chernova, Anand Reghuvaran, Soichiro Nagata, Mateus T. Guerra, John Choi, Soltan Al Chaar, Hiroki Mizuno, Ke Dong, Xin Tian, Reika Ishibe, Barbara Franchin, Paolo Cravedi, Ashwani Kumar, Gabriel Barsotti, Hongmei Shi, Bony De Kumar, Shinobu Smithson, Wenzhi Son · 2026
Read APOL1 risk alleles modulate T cell receptor signaling to promote allograft rejection by John Pell, EM Tanvir, Zeguo Sun, Irene Chernova, Anand Reghuvaran, Soichiro Nagata, Mateus T. Guerra, John Choi, Soltan Al Chaar, Hiroki Mizuno, Ke Dong, Xin Tian, Reika Ishibe, Barbara Franchin, Paolo Cravedi, Ashwani Kumar, Gabriel Barsotti, Hongmei Shi, Bony De Kumar, Shinobu Smithson, Wenzhi Son (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/pmc-13430025.txt.
Description
Pell and a large team investigated why APOL1 risk variants, gene changes common in people of African ancestry, promote kidney transplant rejection beyond their known effects on kidney cells. Working with transgenic mice expressing the normal gene or the G1 and G2 risk versions at natural levels, they focused on T cell behavior.
Mice carrying either risk variant showed stronger CD8 T cell activation and an expanded pool of central memory T cells, the long-lived sentinels of immune memory. Stimulated G1 cells multiplied more and produced more cytokines, effects reversed by blocking APOL1 in the experiments. In mismatched heart transplants, G1 mice accumulated more graft-infiltrating T cells and lost grafts sooner than controls. The mechanism ran through calcium signaling: G1 cells started with depleted internal calcium stores and surged higher on stimulation, making them unusually sensitive to calcium blockers.
Catalog record
| CREATOR | John Pell, EM Tanvir, Zeguo Sun, Irene Chernova, Anand Reghuvaran, Soichiro Nagata, Mateus T. Guerra, John Choi, Soltan Al Chaar, Hiroki Mizuno, Ke Dong, Xin Tian, Reika Ishibe, Barbara Franchin, Paolo Cravedi, Ashwani Kumar, Gabriel Barsotti, Hongmei Shi, Bony De Kumar, Shinobu Smithson, Wenzhi Son |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 59 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |