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Irradiated donor leukocytes promote engraftment of allogeneic bone marrow in major histocompatibility complex mismatched recipients without causing graft-versus-host disease.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Waller, Edmund K. Ship, A. M. Mittelstaedt, Stephen Murray, Todd W. Carter, Roberte Kakhniashvili, Irina Lonial, Sagar Holden, Jeannine T. Boyer, Michael W. |
| Copyright Year | 1999 |
| Abstract | Graft rejection in allogeneic bone marrow transplantation (BMT) can occur when donor and recipient are mismatched at one or more major histocompatibility complex (MHC) loci. Donor T cells can prevent graft rejection, but may cause fatal graft-versus-host disease (GVHD). We tested whether irradiation of allogeneic donor lymphocytes would preserve their graft-facilitating activity while inhibiting their potential for GVHD. Infusions of irradiated allogeneic T cells did not cause GVHD in MHC-mismatched SJL --> (SJL x C57BL6) F1, C57BL6 --> B10.RIII, and C57BL6 --> B10.BR mouse donor --> recipient BMT pairs. The 60-day survival among MHC-mismatched transplant recipients increased from 2% (BM alone) to up to 75% among recipients of BM plus irradiated allogeneic splenocytes. Optimal results were obtained using 50 x 10(6) to 75 x 10(6) irradiated donor splenocytes administered in multiple injections from day -1 to day +1. Recipients of an equal number of nonirradiated MHC-mismatched donor splenocytes uniformly died of acute GVHD. The graft facilitating activity of the irradiated allogeneic splenocytes was mediated by donor T cells. Irradiation to 7.5 Gy increased nuclear NFkappaB in T cells and their allospecific cytotoxicity. Irradiated T cells survived up to 3 days in the BM of MHC-mismatched recipients without proliferation. Recipients of irradiated allogeneic splenocytes and allogeneic BM had stable donor-derived hematopoiesis without a significant representation of donor splenocytes in the T-cell compartment. Irradiated allogeneic T cells thus represent a form of cellular immunotherapy with time-limited biologic activity in vivo that can facilitate allogeneic BMT without causing GVHD. |
| File Format | PDF HTM / HTML |
| DOI | 10.1182/blood.v94.9.3222 |
| PubMed reference number | 10556211 |
| Journal | Medline |
| Volume Number | 94 |
| Issue Number | 9 |
| Alternate Webpage(s) | http://www.bloodjournal.org/content/bloodjournal/94/9/3222.full.pdf?sso-checked=true |
| Alternate Webpage(s) | https://doi.org/10.1182/blood.v94.9.3222 |
| Journal | Blood |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
