Abstract
We developed a nonmyeloablative host conditioning regimen in a mouse model of MHC-mismatched bone marrow transplantation that not only reduces radiation toxicity, but also protects against graft-vs-host disease. The regimen of fractionated irradiation directed to the lymphoid tissues and depletive anti-T cell Abs results in a marked change in the residual host T cells, such that NK1.1+ or DX5+asialo-GM1+ T cells become the predominant T cell subset in the lymphoid tissues of C57BL/6 and BALB/c mice, respectively. The latter "natural suppressor" T cells protect hosts from graft-vs-host disease after the infusion of allogeneic bone marrow and peripheral blood cells that ordinarily kill hosts conditioned with sublethal or lethal total body irradiation. Protected hosts become stable mixed chimeras, but fail to show the early expansion and infiltration of donor T cells in the gut, liver, and blood associated with host tissue injury. Cytokine secretion and adoptive transfer studies using wild-type and IL-4(-/-) mice showed that protection afforded by NK1.1+ and DX5+asialo-GM1+ T cells derived from either donors or hosts conditioned with lymphoid irradiation is dependent on their secretion of high levels of IL-4.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Antigens / biosynthesis*
-
Antigens, Ly
-
Antigens, Surface
-
Bone Marrow Transplantation / immunology
-
Bone Marrow Transplantation / mortality
-
Bone Marrow Transplantation / pathology
-
Cell Division / genetics
-
Cell Division / immunology
-
Cytokines / metabolism
-
Graft vs Host Disease / prevention & control*
-
Immunophenotyping
-
Interleukin-4 / deficiency
-
Interleukin-4 / genetics
-
Interleukin-4 / metabolism
-
Killer Cells, Natural / metabolism
-
Killer Cells, Natural / transplantation*
-
Lectins, C-Type
-
Lymphatic Irradiation* / methods
-
Lymphocyte Count
-
Male
-
Mice
-
Mice, Inbred BALB C
-
Mice, Inbred C57BL
-
Mice, Knockout
-
NK Cell Lectin-Like Receptor Subfamily B
-
Protein Biosynthesis*
-
Proteins*
-
Radiation Chimera / immunology
-
Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
-
T-Lymphocyte Subsets / metabolism
-
T-Lymphocyte Subsets / transplantation*
-
T-Lymphocytes, Regulatory / metabolism
-
T-Lymphocytes, Regulatory / transplantation*
-
Transplantation Conditioning* / methods
Substances
-
Antigens
-
Antigens, Ly
-
Antigens, Surface
-
Cytokines
-
Klrb1c protein, mouse
-
Lectins, C-Type
-
NK Cell Lectin-Like Receptor Subfamily B
-
Proteins
-
Receptors, Antigen, T-Cell, alpha-beta
-
Interleukin-4