Unconventional T Cells Influence Clinical Outcome After Allogeneic Hematopoietic Cell Transplantation

Abstract

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.

Keywords: Acute graft-versus-host disease; Allogeneic hematopoietic cell transplantation (allo-HCT); Mucosal-associated invariant T cells (MAIT); Vδ2+ T cells.