Immune surveillance by autoreactive CD4-positive helper T cells is a common phenomenon in patients with acute myeloid leukemia

The importance of autologous T-cell responses in immune surveillance against acute myeloid leukemia (AML) remains unclear. Therefore, we investigated the presence and functional reactivity of autoreactive T-cell responses against autologous AML blasts.

T cells purified from PB samples harvested from patients during first complete remission were stimulated with autologous AML material harvested at diagnosis. After 12-14 days of coculture, the T cells were restimulated with autologous AML cells, and leukemia-reactive T-cell clones were isolated based on their expression of the activation marker CD137.

We demonstrated that AML-induced autoreactivity was predominantly mediated by CD4 T cells. These autoreactive T cells showed abundant cytokine production, coincided by modest cytotoxic activity. Upon coculture, the autoreactive T cells were able to increase the immunogenicity of the AML blasts. Interestingly, similar AML-directed reactivity was observed using HLA-identical responder T cells from healthy donors.

We demonstrated that the presence of AML-directed autoreactive T cells is a common phenomenon which appears to be part of the general T-cell repertoire also in healthy individuals. This autoreactive AML-directed T-cell response may directly contribute to anti-AML immune surveillance especially in the situation of minimal residual disease, but furthermore the immune-modulatory effect on the AML phenotype may pave the way for other immunological interventions.