Migrating donor T cells after minor histocompatibility antigen (miHAg) mismatch allogeneic hematopoietic cell transplantation (allo-HCT) can be clearly detected in the peripheral blood (PB) for at least 2 weeks before onset of acute graft-versus-host disease (aGVHD). (A) Absolute PB T cell counts for donor CD4+ (◯) and CD8+ (■) T cells after major histocompatibility complex (MHC) mismatch (left panel), miHAg mismatch (middle panel), and syngeneic HCT (right panel) are shown. Three mice per day per group were analyzed (n = 15 per group). In the MHC major mismatch model, only surviving animals could be bled at later timepoints. One experiment out of three is shown. Error bars display means plus or minus SEM. (B) T cell chimerism analysis on indicated timepoints after miHAg mismatch allo-HCT revealed that after day +6 more than 90% of PB CD8+ and CD4+ T cells were of donor T cell origin. Of note, the detection of CD90.1+ T cells only included transferred donor T cells but not donor bone marrow (BM)-derived CD90.2+ T cells. Results for CD8+ and CD4+ T cells of one representative experiment are shown, separately (n = 3). (C) Representative flow cytometry plots display α4β7 integrin and P-selectin ligand expression on donor T cells at indicated timepoints in allogeneic and syngeneic recipients. Numbers in each quadrant represent percentages of all donor T cells. (D) Daily flow cytometry analyses revealed high numbers of cells in the PB expressing α4β7 integrin as well as P-selectin ligand in the miHAg model (■) in comparison to the expression in syngeneic recipients (▽) which stayed constantly low. Donor T cells in the MHC major mismatch model (◯) also strongly upregulated those receptors before mice died of aGVHD. Three mice per day per group were analyzed (n = 15). Graphs show results from one representative experiment out of three. Error bars display means plus or minus SEM. *P ≤0.05.
Bäuerlein et al. BMC Medicine 2013 11:134 doi:10.1186/1741-7015-11-134