Antigen-specific recognition of autologous leukemia cells and allogeneic class-I MHC antigens by IL-2-activated cytotoxic T cells from a patient with acute T-cell leukemia

Abstract

Culturing of leukemic blood lymphocytes from a patient with acute T- cell lymphoblastic leukemia (T-ALL) with interleukin-2 (IL-2) yielded T- cell line AK-1 with a remarkable cytotoxic specificity. This line mediated strong lysis of tumor target lines expressing major histocompatibility complex (MHC) class I antigens, such as Raji, CEM, and Molt-4 cells, but no killing of K562 and Daudi cells, which are deficient in MHC class I. In contrast, lymphokine-activated killer (LAK) cells from normal donors destroyed all these tumor targets, without MHC restriction. Line AK-1, originating from residual normal T cells present in the leukemic blood, lysed autologous leukemic blasts and peripheral blood lymphocytes (PBL) from many but not all allogeneic individuals but failed to kill autologous remission lymphocytes. Destruction of the autologous leukemic targets by AK-1 could be inhibited by unlabeled competitor target cells that were lysed by AK-1, but not by target cells that were not lysed. This suggests that AK-1 specifically recognized an alien determinant on the autologous ALL cells, crossreactive with allogeneic MHC class I antigens. This reactivity with some degree of tumor specificity may be a leukemic equivalent to responses reported for populations of tumor infiltrating lymphocytes (TIL) seen in some solid tumors.

Leukemia‐associated antigenic isoforms induce a specific immune response in children with T‐ALL

“…Thus, repairing the antigen presenting capacity of tumor cells as well as the reversal of tolerance seems to be necessary to elicit a specific immune response 9. With the exception of one case report,10 T‐ALLs have not been analyzed for their immunogenicity.…”