Activation of CD8+ murine T cells from tumor-draining lymph nodes by phorbol dibutyrate plus calcium ionophore.
J Immunother (1991)
; 12(1): 32-40, 1992 Jul.
Article
em En
| MEDLINE
| ID: mdl-1386251
ABSTRACT
When lymphocytes from the lymph nodes draining the site of a progressively growing MCA-105 sarcoma are stimulated in vitro with autologous tumor and low-dose interleukin-2 (IL-2), they will grow and develop the ability to lyse autologous tumor cells in vitro; these lymphocytes can also eradicate tumor metastases in vivo. Phorbol esters and calcium ionophores activate signal transduction pathways in T cells and mimic the events triggered by antigen binding. We therefore sought to determine whether large numbers of MCA-105 tumor-specific, therapeutically active T cells could be obtained from MCA-105 draining lymph nodes (DLNs) following a brief exposure to phorbol dibutyrate (PDBu) and ionomycin (Io). DLN cells primarily stimulated with autologous tumor, followed by a secondary stimulation with PDBu-Io and cultured in 20 U/ml IL-2, demonstrated marked expansion of cell numbers during 3 weeks in culture, had moderate cytolytic activity [37% at effectortarget ratio (ET) = 801], and were all CD8+ T cells. In contrast, DLN cells stimulated primarily with PDBu-Io and cultured in 20 U/ml IL-2 demonstrated at least 8-10-fold greater growth than antigen-stimulated DLN cells during 3 weeks, were moderately cytolytic (31% at ET = 801), and were a mixed population of CD8+ and CD4+ T lymphocytes. DLN cells that were expanded by either protocol, like cells stimulated repeatedly in vitro with tumor cells, could eliminate MCA-105 pulmonary metastases when given with IL-2 in an adoptive immunotherapy model. DLN cells stimulated primarily with PDBu-Io completely eradicated MCA-105 metastases but had no in vivo antitumor activity against the syngeneic B16 melanoma or MCA-203 sarcoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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Base de dados:
MEDLINE
Assunto principal:
Sarcoma Experimental
/
Ativação Linfocitária
/
Dibutirato de 12,13-Forbol
/
Ionomicina
/
Linfócitos T Reguladores
/
Linfonodos
Tipo de estudo:
Guideline
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Immunother (1991)
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
NEOPLASIAS
Ano de publicação:
1992
Tipo de documento:
Article