Irradiation and IL-15 promote loss of CD8 T-cell tolerance in response to lymphopenia.
Blood
; 115(11): 2196-202, 2010 Mar 18.
Article
em En
| MEDLINE
| ID: mdl-20075162
ABSTRACT
Functional inactivation of self-reactive T lymphocytes contributes to the maintenance of immunologic self-tolerance. At the same time, tolerance induction limits immune responses against tumors expressing tolerizing self-antigens. Some cancer therapies include the adoptive transfer of tumor-reactive T lymphocytes into lymphopenic patients. Lymphopenia provides an activation signal to T lymphocytes, which undergo lymphopenia-induced proliferation (LIP), acquire effector functions, and reject tumors. However, it is so far unknown to which extent LIP may result in reversal of established antigen-specific CD8 T-cell tolerance. Here, we report that neonatally induced dominant CD8 T-cell tolerance remained stable under lymphopenic conditions also in the presence of systemic inflammation induced by Toll-like receptor ligands. However, when lymphopenic recipients were irradiated, the tolerant status was lost, because CD8 T cells acquired effector functions in an interleukin-15-dependent fashion and efficiently rejected tumors. In conclusion, we show that lymphopenia is not sufficient to break CD8 T-cell tolerance. Furthermore, we demonstrate that pretreatment regimens are crucial to circumvent this problem and to optimize adoptive T-cell therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Irradiação Corporal Total
/
Linfócitos T CD8-Positivos
/
Interleucina-15
/
Tolerância Imunológica
/
Linfopenia
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article