Graft-versus-host-disease-associated thymic damage results in the appearance of T cell clones with anti-host reactivity.
Transplantation
; 69(3): 446-9, 2000 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-10706060
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Imunologia de Transplantes
/
Subpopulações de Linfócitos T
/
Transplante de Medula Óssea
/
Doença Enxerto-Hospedeiro
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article