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Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Bergen, Cornelis A. M. Van Luxemburg-Heijs, Simone A. P. Van Wreede, Liesbeth C. De Eefting, Matthijs Borne, Peter A. Von Dem Balen, Peter Van Heemskerk, Mirjam H. M. Mulder, A. Dirks- Claas, Fransiscus H. J. Navarrete, Marcelo A. Honders, Wilhelmina M. Rutten, Caroline Elisabeth Veelken, Hendrik Dr Jedema, Inge Halkes, Constantijn J. M. Griffioen, Marieke Falkenburg, J. H. Frederik |
| Copyright Year | 2017 |
| Abstract | 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. |
| Starting Page | 517 |
| Ending Page | 529 |
| Page Count | 13 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://www.jci.org/articles/view/86175/version/2/pdf/render |
| Alternate Webpage(s) | http://www.jci.org/articles/view/86175/version/2/pdf/render |
| Alternate Webpage(s) | http://www.jci.org/articles/view/86175/version/1/pdf/render |
| PubMed reference number | 28067665v1 |
| Alternate Webpage(s) | https://doi.org/10.1172/JCI86175 |
| DOI | 10.1172/JCI86175 |
| Journal | The Journal of clinical investigation |
| Volume Number | 127 |
| Issue Number | 2 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Chronic Lymphocytic Leukemia Donor Lymphocyte Infusion Graft versus host disease prophylaxis/therapy Graft vs Leukemia Effect Leukemia, B-Cell Minor Histocompatibility Antigens Patients Stem cells T-Lymphocyte Transplanted tissue XIAP gene cytokine |
| Content Type | Text |
| Resource Type | Article |
