T-lymphocyte production of macrophage inflammatory protein-1α is critical to the recruitment of CD8+ T cells to the liver, lung, and spleen during graft-versus-host disease

• Published in: Blood Vol. 96; no. 9; pp. 2973 - 2980
• Main Authors: Serody, Jonathan S., Burkett, Susan E., Panoskaltsis-Mortari, Angela, Ng-Cashin, Judith, McMahon, Eileen, Matsushima, Glenn K., Lira, Sergio A., Cook, Donald N., Blazar, Bruce R.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.11.2000; The Americain Society of Hematology
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Medical sciences; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Immunopathology; Animal model; Immune response; Stem cell; Rodentia; Hematopoietic cell; Homograft; Graft versus host reaction; Macrophage inflammatory protein 1alpha; Cell subpopulation; Chemokine; Vertebrata; Mammalia; Donor; Mouse; Animal; T-Lymphocyte; Graft; Suppressive cell
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V96.9.2973

To investigate the mechanism by which macrophage inflammatory protein-1α (MIP-1α) affects graft-versus-host disease (GVHD), the expression and function of MIP-1α in 2 murine models of GVHD were evaluated. In irradiated class I and class II disparate recipients, the expression of messenger RNA (mRNA) and protein for MIP-1α was significantly increased in GVHD target organs after transfer of allogeneic lymphocytes compared to syngeneic lymphocytes. When lymphocytes unable to make MIP-1α were transferred, there was a decrease in the production of MIP-1α in the liver, lung, and spleen of bm1 (B6.C-H2bm1/By) and bm12 (B6.C-H2bm12/KhEg) recipients compared to the transfer of wild-type splenocytes. At day 6 there was a 4-fold decrease in the number of transferred CD8+ T cells in the lung and approximately a 2-fold decrease in the number of CD8+ T cells in the liver and spleen in bm1 recipients after transfer of MIP-1α–deficient (MIP-1α−/−) splenocytes compared to wild-type (MIP-1α+/+) splenocytes. These differences persisted for 13 days after splenocyte transfer. In contrast, the number of donor CD4+ T cells found in the liver and lung was significantly increased after the transfer of MIP-1α−/− compared to wild-type splenocytes in bm12 recipients from day 6 through day 10. Thus, the transfer of allogeneic T cells was associated with the enhanced expression of MIP-1α in both a class I and class II mismatch setting. However, the increased expression only led to enhanced recruitment of CD8+, but not CD4+, donor T cells. Production of MIP-1α by donor T cells is important in the occurrence of GVHD and functions in a tissue-dependent fashion.