Graft-versus-host-disease-associated thymic damage results in the appearance of T cell clones with anti-host reactivity.
BACKGROUND
We studied whether T-cell clones, which appear in the periphery as a result of the failure of thymic negative selection during graft-versus-host disease (GVHD), have any in vivo anti-host reactivity and can cause GVHD in an adoptive transfer model.


METHODS
We performed our studies in a murine model (B10.BR into CBA/J) for allogeneic bone marrow transplantation with major histocompatibility complex-matched and minor histocompatibility antigen-mismatched unrelated donors and unique Vbeta T-cell deletion patterns in donors and recipients.


RESULTS
GVHD resulted in the appearance of Vbeta6+ T cells as a result of a loss of negative selection. We found that Vbeta6+ T cells from normal donors proliferated in vitro and in vivo. Depletion of Vbeta6+ T cells from the donor T-cell inoculum resulted in less GVHD morbidity and a decrease in the loss of thymic cellularity. To test the anti-host reactivity of de novo generated Vbeta6+ T cells in animals with GVHD, we developed an adoptive transfer model of splenic T cells from CBA/J host animals with GVHD into sublethally irradiated CBA/J recipients Depletion of Vbeta6+ T cells from the splenic T cells before adoptive transfer could significantly decrease the transient GVHD morbidity in the sublethally irradiated hosts.


CONCLUSIONS
Our data indicate that GVHD-associated thymic damage results in a loss of thymic negative selection, which leads to the appearance of T-cell clones with anti-host reactivity in vitro and in vivo.
van den Brink
M R
MR
Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA. m-van-den-brink@ski.mskcc.org
Moore
E
E
Ferrara
J L
JL
Burakoff
S J
SJ
D000818:Animals; D017951:Antigen Presentation; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014181:Transplantation Immunology; D014184:Transplantation, Homologous