التفاصيل البيبلوغرافية
| العنوان: |
Tumor-specific T cells signal tumor destruction via the lymphotoxin β receptor |
| المؤلفون: |
Winter, Hauke, van den Engel, Natasja K, Poehlein, Christian H, Hatz, Rudolf A, Fox, Bernard A, Hu, Hong-Ming |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2007 |
| المجموعة: |
BioMed Central |
| الوصف: |
Background Previously, we reported that adoptively transferred perforin k/o (PKO), and IFN-γ k/o (GKO), or perforin/IFN-γ double k/o (PKO/GKO) effector T cells mediated regression of B16BL6-D5 (D5) pulmonary metastases and showed that TNF receptor signaling played a critical role in mediating tumor regression. In this report we investigated the role of lymphotoxin-α (LT-α) as a potential effector molecules of tumor-specific effector T cells. Methods Effector T cells were generated from tumor vaccine-draining lymph node (TVDLN) of wt, GKO, LT-α deficient (LKO), or PKO/GKO mice and tested for their ability to mediate regression of D5 pulmonary metastases in the presence or absence of LT-βR-Fc fusion protein or anti-IFN-γ antibody. Chemokine production by D5 tumor cells was determined by ELISA, RT-PCR and Chemotaxis assays. Results Stimulated effector T cells from wt, GKO, or PKO/GKO mice expressed ligands for LT-β receptor (LT-βR). D5 tumor cells were found to constitutively express the LT-βR. Administration of LT-βR-Fc fusion protein completely abrogated the therapeutic efficacy of GKO or PKO/GKO but not wt effector T cells (p < 0.05). Consistent with this observation, therapeutic efficacy of effector T cells deficient in LT-α, was greatly reduced when IFN-γ production was neutralized. While recombinant LT-α1β2 did not induce apoptosis of D5 tumor cells in vitro, it induced secretion of chemokines by D5 that promoted migration of macrophages. Conclusion The contribution of LT-α expression by effector T cells to anti-tumor activity in vivo was not discernable when wt effector T cells were studied. However, the contribution of LT-β R signaling was identified for GKO or PKO/GKO effector T cells. Since LT-α does not directly induce killing of D5 tumor cells in vitro, but does stimulate D5 tumor cells to secrete chemokines, these data suggest a model where LT-α expression by tumor-specific effector T cells interacts via cross-linking of the LT-βR on tumor cells to induce secretion of chemokines that are ... |
| نوع الوثيقة: |
report |
| اللغة: |
English |
| العلاقة: |
http://www.translational-medicine.com/content/5/1/14Test |
| الإتاحة: |
http://www.translational-medicine.com/content/5/1/14Test |
| حقوق: |
Copyright 2007 Winter et al; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.4DEC8B42 |
| قاعدة البيانات: |
BASE |
