Transplantation of polarized type 2 donor T cells reduces mortality caused by experimental graft-versus-host disease.
Acute graft-versus-host disease (GVHD) is thought to be initiated by alloreactive type 1 T cells that secrete gamma-interferon (IFN-gamma). IFN-gamma induces the production of inflammatory cytokines, e.g., tumor necrosis factor-alpha and interleukin (IL)-1, which are the distal mediators of GVHD. We demonstrate that the transplantation of polarized type 2 murine T cells (i.e., cells secreting IL-4 but not IFN-gamma) together with T-cell-depleted bone marrow results in a significant increase in survival (P<0.001) after bone marrow transplantation across minor histocompatibility barriers (B10.BR-->CBA/J). Further analysis demonstrated that increased survival in recipients of polarized type 2 T cells correlated with diminished production of both IFN-gamma and tumor necrosis factor-alpha but with increases in IL-4 2 weeks after transplantation. Despite improved survival, histologic changes of GVHD were evident in oral mucosal and hepatic tissues at 7 weeks after bone marrow transplantation. These data provide further evidence that inflammatory cytokines in the immediate posttransplant period are pivotal to the development of mortality but that they do not correlate with individual target organ damage.
Krenger
W
W
Division of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cooke
K R
KR
Crawford
J M
JM
Sonis
S T
ST
Simmons
R
R
Pan
L
L
Delmonte
J
J
Karandikar
M
M
Ferrara
J L
JL
D019264:Adoptive Transfer; D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000401:mortality; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D014184:Transplantation, Homologous
D015847:Interleukin-4