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Interleukin-12 Inhibits Graft-Versus-Host Disease Through an Fas-Mediated Mechanism Associated With Alterations in Donor T-Cell Activation and Expansion
| Content Provider | Scilit |
|---|---|
| Author | Dey, Bimalangshu R. Yang, Yong-Guang Szot, Gregory L. Pearson, Denise A. Sykes, Megan |
| Copyright Year | 1998 |
| Description | We have recently made the paradoxical observation that a single injection of recombinant murine interleukin-12 (IL-12) on the day of bone marrow transplantation (BMT) inhibits graft-versus-host disease (GVHD) in lethally irradiated mice receiving fully major histocompatability complex (MHC)-mismatched bone marrow and spleen cells. We have now examined the mechanism of this effect of IL-12 on acute GVHD. By day 4 post-BMT, IL-12–treated mice showed marked reductions in splenic donor CD4+ and CD8+ T cells compared with GVHD controls. Expression of the early activation markers IL-2R alpha chain (CD25) and CD69 on splenic donor CD4+ cells was considerably higher at early time points (36 and 72 hours post-BMT) in IL-12–treated mice compared with GVHD controls. However, the later, GVHD-associated increase in CD25 and very late antigen-4 (VLA-4) expression on donor T cells was greatly depressed in IL-12–protected mice compared with GVHD controls. The marked GVHD-associated expansion of host-reactive T helper cells by day 4 was also completely inhibited in the IL-12–treated group. Expression of Fas was increased on donor CD4 cells of IL-12–treated mice compared with those of controls on days 3 through 7 post-BMT. Furthermore, the ability of IL-12 to protect against GVHD was at least partially dependent on the ability of donor cells to express functional Fas molecules. We conclude that IL-12 treatment at the time of BMT markedly perturbs the activation of alloreactive donor CD4+ T cells that play a critical role in the pathogenesis of acute GVHD. We hypothesize that these perturbations culminate in Fas-dependent apoptosis of donor T cells, thus impeding their expansion and their GVHD-promoting activity. |
| Related Links | https://ashpublications.org/blood/article-pdf/91/9/3315/1045944/3315.pdf |
| Ending Page | 3322 |
| Page Count | 8 |
| Starting Page | 3315 |
| DOI | 10.1182/blood.v91.9.3315 |
| Journal | Blood |
| Issue Number | 9 |
| Volume Number | 91 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 1998-05-01 |
| Access Restriction | Open |
| Subject Keyword | Transplantation Apoptosis Treatment Bone Marrow Functional Antigen Acute Gvhd Bmt Donor Journal: Blood (Vol- 108, Issue- 9) |
| Content Type | Text |
| Resource Type | Article |
