Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response

van Bergen, Cornelis A. M.; van Luxemburg-Heijs, Simone A. P.; de Wreede, Liesbeth C.; Eefting, Matthijs; von dem Borne, Peter A.; van Balen, Peter; Heemskerk, Mirjam H. M.; Mulder, Arend; Claas, Fransiscus H. J.; Navarrete, Marcelo; Honders, Wilhelmina M.; Rutten, Caroline E.; Veelken, Hendrik; Jedema, Inge; Halkes, Constantijn J. M.; Griffioen, Marieke; Falkenburg, J. H. Frederik

doi:https://doi.org/10.1172/jci86175

Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response

van Bergen, Cornelis A. M.

[1];

van Luxemburg-Heijs, Simone A. P.

[1];

de Wreede, Liesbeth C.

[2];

Eefting, Matthijs

[1];

von dem Borne, Peter A.

[1];

van Balen, Peter

[1];

Heemskerk, Mirjam H. M.

[1];

Mulder, Arend

[1];

Claas, Fransiscus H. J.

[1];

Navarrete, Marcelo

[3];

Honders, Wilhelmina M.

[1];

Rutten, Caroline E.

[1];

Veelken, Hendrik

[1];

Jedema, Inge

[1];

Halkes, Constantijn J. M.

[1];

Griffioen, Marieke

[1];

Falkenburg, J. H. Frederik

[1]

¹
Leiden University - Excl LUMC
²
Leiden University
³
Escuela de Medicina

DOI

https://doi.org/10.1172/jci86175

Date Issued

2017-02-01

Type

Artículo

Journal

Journal of Clinical Investigation

ISSN

0021-9738

1558-8238

Open Access

bronze

Volume

127

Start page

517

End page

529

Links

https://arca.umag.cl/handle/123456789/15759

Patients with leukemia who receive a T cell-depleted allogeneic stem cell graft followed by postponed donor lymphocyte infusion (DLI) can experience graft-versus-leukemia (GVL) reactivity, with a lower risk of graft-versus-host disease (GVHD). Here, we have investigated the magnitude, diversity, and specificity of alloreactive CD8 T cells in patients who developed GVL reactivity after DLI in the absence or presence of GVHD. We observed a lower magnitude and diversity of CD8 T cells for minor histocompatibility antigens (MiHAs) in patients with selective GVL reactivity without GVHD. Furthermore, we demonstrated that MiHA-specific T cell clones from patients with selective GVL reactivity showed lower reactivity against nonhematopoietic cells, even when pretreated with inflammatory cytokines. Expression analysis of MiHA-encoding genes showed that similar types of antigens were recognized in both patient groups, but in patients who developed GVHD, T cell reactivity was skewed to target broadly expressed MiHAs. As an inflammatory environment can render nonhematopoietic cells susceptible to T cell recognition, prevention of such circumstances favors induction of selective GVL reactivity without development of GVHD.

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