Unconventional T Cells Influence Clinical Outcome After Allogeneic Hematopoietic Cell Transplantation

We evaluated the impact of early recovery of mucosal-associated invariant T cells (MAIT) and gamma-delta (γδ) T cells, especially Vδ2⁺ T cells, on the clinical outcomes of 76 patients who underwent allogeneic hematopoietic cell transplantation (allo-HCT). MAIT cells were identified at day 20–30 post-transplant using flow cytometry and defined as CD3⁺ TCRVα7.2⁺CD161⁺. Two subsets of Vδ2⁺ T cells were analyzed according to the expression of CD26. The cytotoxicity profile of MAIT and Vδ2⁺ T cells was analyzed according to the intracellular expression of perforin and granzyme B, and intracellular IFN-γ was evaluated after in vitro activation. CD26⁺Vδ2⁺ T cells displayed higher intracellular levels of IFN-γ, whereas CD26⁻ Vδ2⁺ T were found to be more cytotoxic. Moreover, MAIT cell frequency was correlated with the frequency of Vδ2⁺ T cells with a better correlation observed with Vδ2⁺CD26⁺ than with the Vδ2⁺CD26⁻ T cell subset. By using the composite endpoint graft-versus-host disease (GvHD)-free, relapse-free survival (GRFS) as the primary endpoint, we found that patients with a higher MAIT cell frequency at day 20–30 after allo-HCT had a significantly increased GRFS and a better overall survival (OS) and disease-free survival (DFS). Moreover, patients with a low CD69 expression by MAIT cells had an increased cumulative incidence of grade 2–4 acute GvHD (aGvHD). These results suggest that MAIT cell reconstitution may provide mitigating effects early after allo-HCT depending on their activation markers and functional status. Patients with a high frequency of Vδ2⁺CD26⁺ T cells had a significantly higher GRFS, OS and DFS, but there was no impact on cumulative incidence of grade 2–4 aGVHD, non-relapse mortality and relapse. These results revealed that the impact of Vδ2⁺ T cells on the success of allo-HCT may vary according to the frequency of the CD26⁺ subset.