[논문]The effect of anti-CD3-immunotoxin on T lymphocyte function in vitro

doi:10.1016/S0966-3274(98)80035-X

[해외논문] The effect of anti-CD3-immunotoxin on T lymphocyte function in vitro

Transplant immunology, v.6 no.1, 1998년, pp.53 - 59

Meng, Gang (University of Alabama at Birmingham, Birmingham, AlabamaU.S.A.) , Jiang, Yi (University of Alabama at Birmingham, Birmingham, AlabamaU.S.A.) , Hubbard, William (University of Alabama at Birmingham, Birmingham, AlabamaU.S.A.) , Thomas, Judith M (Address for correspondence: JM Thomas, Division of Immunology, Department of Surgery, Transplant Center BDB #802, 1808 7th Avenue South, Birmingham, AL, 35294, USA)

Abstract ▼ AI-Helper

AbstractRecent advances in the design of immunotoxins (IT) have yielded significant improvements. FN18-CRM9, a construct of anti-Cd3ε mAb FN18 and mutated diphtheria toxin CRM9 has exhibited high specificity, low systemic toxicity and unusual efficacy compared to previous iterations of immunotoxins. Others and we have examined anti-CD3-IT for the purpose of inducing immunological tolerance through selective ablation of T cells in rhesus macaques and have obtained encouraging results. In order to characterize its mode of action, we have examined its effects on peripheral blood and lymph node T cell killing in vitro. We have studied the cytotoxic mechanism induced by this anti-CD3-IT as well as its effects on proliferation, phenotypic changes and cytokine production (IL2, IFNγ and TNFα). The results indicate that anti-CD3-IT was highly specific for T cell killing at doses as low as 1 × 106 μg/ml and showed a maximal effect at 48 h after exposure. The toxicity was restricted to T cells, as B cells and other bystander cells were spared. This immunotoxin was shown to induce T cell apoptosis, as assessed by TUNEL assay, DNA content and cytotoxicity. Fas expression was upregulated on T cells within 24 h after in vitro exposure to anti-CD3-IT, suggesting an early T cell activation phase prior to T cell death. T cell killing was manifest as an early cell cycle arrest at the G1/S phase transition, which appeared to virtually eliminate the production of cytokines. These finding corroborate the temporal, specificity and quantitative patterns for anti-CD3 immunotoxin administration previously observed in vivo.

참고문헌 (29)

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DOI : 10.1016/S0966-3274(98)80035-X
OCLC ECO : 저널
Elsevier : 저널 > 논문

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[해외논문] The effect of anti-CD3-immunotoxin on T lymphocyte function in vitro

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