Leukemic CD3⁺ LGL share functional properties with their CD8⁺CD57⁺ cell counterpart expanded after BMT

Abstract

Leukemic T-LGL (large granular lymphocyte) composed of clonal CD3⁺TCRαβ⁺CD8⁺CD57⁺ cells were compared with oligoclonally CD3⁺CD8^hi+CD57⁻ lymphocytes expanded after BMT. Leukemic CD3⁺CD8^hi+CD57⁺ LGL showed several phenotypic differences such as an upregulation of CD16 and adhesion molecules (mainly CD11c, CD58 and CD54), activation markers and an exclusive CD45RA isoform expression. Unstimulated CD3⁺CD8⁺CD57⁺ LGL from both leukemic and BMT donors spontaneously developed an ex vivo CTL-like CD3-redirected cytotoxicity but no NK cell activity. Different stimuli (PHA, PMA or rhIL-2) induced similar cytotoxic profiles after a 6-day culture involving a CD3-redirected lysis predominating over a low NK cell activity. However, culture of leukemic LGL with these stimuli allowed either a 2 week persistence (PMA or rhIL-2) of CD8⁺CD57⁺ LGL or their disappearance after 3 days (PHA). Furthermore, leukemic CD8^hi+CD57⁺ T lymphocytes produced an inhibitor of cytotoxic functions as previously described for BMT recipients' CD8⁺CD57⁺ cells. Thus, despite some phenotypic differences between both cell sources, leukemic CD57⁺ T-LGL display the same functional characteristics of cytotoxic effector and immunoregulatory T cells as CD8⁺CD57⁺ T cells from BMT recipients which might represent their normal counterpart.