title: T-lymphocyte production of macrophage inflammatory protein-1alpha is critical to the recruitment of CD8(+) T cells to the liver, lung, and spleen during graft-versus-host disease.
abstract: To investigate the mechanism by which macrophage inflammatory protein-1alpha (MIP-1alpha) affects graft-versus-host disease (GVHD), the expression and function of MIP-1alpha 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-1alpha was significantly increased in GVHD target organs after transfer of allogeneic lymphocytes compared to syngeneic lymphocytes. When lymphocytes unable to make MIP-1alpha were transferred, there was a decrease in the production of MIP-1alpha in the liver, lung, and spleen of bm1 (B6.C-H2(bm1)/By) and bm12 (B6.C-H2(bm12)/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-1alpha-deficient (MIP-1alpha(-/-)) splenocytes compared to wild-type (MIP-1alpha(+/+)) 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-1alpha(-/-) 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-1alpha 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-1alpha by donor T cells is important in the occurrence of GVHD and functions in a tissue-dependent fashion.
authors.affiliation: Departments of Medicine, Microbiology, and Immunology, University of North Carolina School of Medicine, the Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599-7295, USA. serody@med.unc.edu
authors.forename: J S
authors.initials: JS
authors.lastname: Serody
authors.forename: S E
authors.initials: SE
authors.lastname: Burkett
authors.forename: A
authors.initials: A
authors.lastname: Panoskaltsis-Mortari
authors.forename: J
authors.initials: J
authors.lastname: Ng-Cashin
authors.forename: E
authors.initials: E
authors.lastname: McMahon
authors.forename: G K
authors.initials: GK
authors.lastname: Matsushima
authors.forename: S A
authors.initials: SA
authors.lastname: Lira
authors.forename: D N
authors.initials: DN
authors.lastname: Cook
authors.forename: B R
authors.initials: BR
authors.lastname: Blazar
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000235:genetics*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000276:immunology*; D049452:Green Fluorescent Proteins; D008099:Liver / Q000276:immunology*; D008164:Luminescent Proteins / Q000235:genetics; D008168:Lung / Q000276:immunology*; D017710:Lymphocyte Transfusion; D019402:Macrophage Inflammatory Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D008164:Luminescent Proteins; D019402:Macrophage Inflammatory Proteins; D049452:Green Fluorescent Proteins