Some T cells in supercentenarians form large clones of immune “killer” cells

Some T cells in supercentenarians form large clones of immune “killer” cells

On August 19, Kosuke Hashimoto’s team published a comparison of blood T cells from 28 older adults. People over 110 had a higher proportion of CD4 CTLs, a distinct type of T cell that can attack infected or dangerously altered cells. The data also allowed the researchers to reconstruct the likely sequence in which these cells develop.

The same group first identified CD4 CTLs in seven supercentenarians in 2019. In an article published on August 19, the researchers examined how this population changes with age. They compared eight people aged 70–99, ten centenarians, and ten people over 110. The median proportion of CD4 CTLs among all T cells in these groups was 4.0%, 9.6%, and 17.6%, respectively.

CD4 cells usually coordinate the immune response. Some activate a cytotoxic program and begin producing proteins that T cells use to kill infected or dangerously altered cells. To determine how this transition occurs, the team measured the active genes in each cell, the proteins on its surface, and the sequence of its T-cell receptor, the molecule that the cell uses to recognize its target.

Cells with the same receptor form a clone, which means that they descend from the same original cell. The authors identified an intermediate stage between conventional CD4 cells and CD4 CTLs. A cell first lost the surface marker CD27 while retaining CD28, then fully activated the cytotoxic program. The position of these cells between the two groups, together with flow cytometry and RNA analysis, supports this sequence of states.

Each participant’s largest clone had its own receptor sequence and accounted, on average, for one-third of all their CD4 CTLs. The authors compared a short segment of these receptors with a large sequence database. Among the expanded clones, 32 of 36 matches occurred in samples from patients with cancer. These matches with tumor-associated repertoires left the authors with an unresolved question: which persistent targets keep these individual clones active.