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

Leukemic T-LGL (large granular lymphocyte) composed of clonal CD3(+)TCR alpha beta(+)CD8(+)CD57(+) cells were compared with oligoclonally CD3(+)CD8(+)CD57(-) lymphocytes expanded after BMT. Leukemic CD3(+)CD8(hl+)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 rhlL-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 rhlL-2) of CD8(+)CD57(+) LGL or their disappearance after 3 days (PHA). Furthermore, leukemic CD8(hl+)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.