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

International audienceLeukemic T-LGL (large granular lymphocyte) composed of clonal CD3+ TCR alphabeta+ CD8+ CD57+ cells were compared with oligoclonally CD3+ CD8hi+ CD57- lymphocytes expanded after BMT. Leukemic CD3+ CD8hi+ 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 CD8hi+ 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

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

International audienceLeukemic T-LGL (large granular lymphocyte) composed of clonal CD3+ TCR alphabeta+ CD8+ CD57+ cells were compared with oligoclonally CD3+ CD8hi+ CD57- lymphocytes expanded after BMT. Leukemic CD3+ CD8hi+ 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 CD8hi+ 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

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abstract in Fundamental & Clinical Pharmacology , Volume 21, Number s

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

International audienceLeukemic T-LGL (large granular lymphocyte) composed of clonal CD3+ TCR alphabeta+ CD8+ CD57+ cells were compared with oligoclonally CD3+ CD8hi+ CD57- lymphocytes expanded after BMT. Leukemic CD3+ CD8hi+ 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 CD8hi+ 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