Cytotoxic effector function of CD4-independent, CD8(+) T cells is mediated by TNF-α/TNFR.
Transplantation
; 94(11): 1103-10, 2012 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-23222736
ABSTRACT
BACKGROUND:
Liver parenchymal cell allografts initiate both CD4-dependent and CD4-independent, CD8(+) T cell-mediated acute rejection pathways. The magnitude of allospecific CD8(+) T cell in vivo cytotoxic effector function is maximal when primed in the presence of CD4(+) T cells. The current studies were conducted to determine if and how CD4(+) T cells might influence cytotoxic effector mechanisms.METHODS:
Mice were transplanted with allogeneic hepatocytes. In vivo cytotoxicity assays and various gene-deficient recipient mice and target cells were used to determine the development of Fas-, TNF-α-, and perforin-dependent cytotoxic effector mechanisms after transplantation.RESULTS:
CD8(+) T cells maturing in CD4-sufficient hepatocyte recipients develop multiple (Fas-, TNF-α-, and perforin-mediated) cytotoxic mechanisms. However, CD8(+) T cells, maturing in the absence of CD4(+) T cells, mediate cytotoxicity and transplant rejection that is exclusively TNF-α/TNFR-dependent. To determine the kinetics of CD4-mediated help, CD4(+) T cells were adoptively transferred into CD4-deficient mice at various times posttransplant. The maximal influence of CD4(+) T cells on the magnitude of CD8-mediated in vivo allocytotoxicityf occurs within 48 hours.CONCLUSION:
The implication of these studies is that interference of CD4(+) T cell function by disease or immunotherapy will have downstream consequences on both the magnitude of allocytotoxicity as well as the cytotoxic effector mechanisms used by allospecific CD8(+) cytolytic T cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Transplante de Fígado
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Fator de Necrose Tumoral alfa
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Receptores do Fator de Necrose Tumoral
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Linfócitos T CD8-Positivos
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Hepatócitos
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Citotoxicidade Imunológica
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Rejeição de Enxerto
Limite:
Animals
Idioma:
En
Revista:
Transplantation
Ano de publicação:
2012
Tipo de documento:
Article