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Interleukin-2 inhibits graft-versus-host disease-promoting activity of CD4+ cells while preserving CD4- and CD8-mediated graft-versus-leukemia effects
| Content Provider | Scilit |
|---|---|
| Author | Sykes, M. Harty, Mw Szot, Gl Pearson, Da |
| Copyright Year | 1994 |
| Description | We have recently shown that a short course of high-dose interleukin-2 (IL-2) can markedly inhibit the graft-versus-host disease (GVHD)- promoting activity of donor CD4+ T cells. The difficulty in dissociating GVHD-promoting from graft-versus-leukemia (GVL) effects of alloreactive donor T cells currently prevents clinical bone marrow transplantation (BMT) from fulfilling its full potential. To test the capacity of IL-2 treatment to promote such a dissociation, we have developed a new murine transplantable acute myelogenous leukemia model using a class II major histocompatibility complex-positive BALB/c Moloney murine leukemia virus-induced promonocytic leukemia, 2B-4–2. BALB/c mice receiving 2.5 x 10(5) 2B-4–2 cells intravenously 1 week before irradiation and syngeneic BMT died from leukemia within 2 to 4 weeks after BMT. Administration of syngeneic spleen cells and/or a 2.5- day course of IL-2 treatment alone did not inhibit leukemic mortality. In contrast, administration of non-T-cell-depleted fully allogeneic B10 (H-2b) spleen cells and T-cell-depleted B10 marrow led to a significant delay in leukemic mortality in IL-2-treated mice. In these animals GVHD was inhibited by IL-2 treatment. GVL effects were mediated entirely by donor CD4+ and CD8+ T cells. Remarkably, IL-2 administration did not diminish the magnitude of the GVL effect of either T-cell subset. This was surprising, because CD4-mediated GVHD was inhibited in the same animals in which CD4-mediated GVL effects were not reduced by IL-2 treatment. These results suggest a novel mechanism by which GVHD and GVL effects of a single unprimed alloreactive T-cell subset can be dissociated; different CD4 activities promote GVHD and GVL effects, and the former, but not the latter activities are inhibited by treatment with IL-2. |
| Related Links | https://ashpublications.org/blood/article-pdf/83/9/2560/613464/2560.pdf |
| Ending Page | 2569 |
| Page Count | 10 |
| Starting Page | 2560 |
| DOI | 10.1182/blood.v83.9.2560.2560 |
| Journal | Blood |
| Issue Number | 9 |
| Volume Number | 83 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 1994-05-01 |
| Access Restriction | Open |
| Subject Keyword | Research and Experimental Medicine Treatment Bone Marrow Cd4 Alloreactive Cd8 Dissociated Gvhd Leukemia Graft Journal: Blood (Vol- 108, Issue- 9) |
| Content Type | Text |
| Resource Type | Article |
