Activation and preferential expansion of rat cytotoxic (CD8) T cells in vitro and in vivo with a bispecific (anti-TCR alpha/beta x anti-CD2) F(ab')2 antibody
| العنوان: | Activation and preferential expansion of rat cytotoxic (CD8) T cells in vitro and in vivo with a bispecific (anti-TCR alpha/beta x anti-CD2) F(ab')2 antibody |
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| المؤلفون: | A L Tutt, R Reid, B S Wilkins, M J Glennie |
| المصدر: | The Journal of Immunology. 155:2960-2971 |
| بيانات النشر: | The American Association of Immunologists, 1995. |
| سنة النشر: | 1995 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | We show that a bispecific F(ab')2 Ab (BsAb), which cross-links the TCR to CD2 ([anti-CD2 x anti-TCR]) and is highly mitogenic in vitro, also induces marked T cell activation and proliferation when given as a small single dose (50 to 100 micrograms) to rats. Interestingly, the proliferation appeared selective for CD8 cells, increasing this compartment more than 20 times over 72 h. This resulted in a three- to fourfold increase in spleen weight, with histologic evidence of T-zone and red pulp expansion by CD8+ blast cells. Such changes were in striking contrast to those seen after a similar amount of the parent IgG anti-TCR mAb, R73, which, while inducing a transient increase in CD25+ cells, failed to alter the lymphocyte composition. The mitogenic activity of the BsAb was totally dependent on its ability to cross-link CD2 and the TCR, hence a mixture of anti-CD2 and anti-TCR F(ab')2 fragments was without effect in vitro or in vivo. Unlike normal rat T cells or those taken from R73 IgG-treated rats, blood and splenic T cells recovered from BsAb-treated rats were highly cytotoxic against R73 hybridoma targets that express surface anti-TCR mAb and consequently trigger the lytic activity of activated CTL or a rat lymphoma line, LAMA (Thy-1+), using a second BsAb, [anti-TCR x anti-Thy-1], to retarget the CTL. This latter assay provides the basis for a future two-stage targeting strategy for cancer immunotherapy in which a mitogenic BsAb would be given to patients to activate CTL nonspecifically, and then, at an appropriate time, a second BsAb [anti-TCR x antitumor] would be given to deliver activated cells to the tumor target cells. |
| تدمد: | 1550-6606 0022-1767 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::993f772b7ae686df1444a272c842770f https://doi.org/10.4049/jimmunol.155.6.2960 |
| رقم الأكسشن: | edsair.doi...........993f772b7ae686df1444a272c842770f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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