Analysis of CD3-antibody-mediated inhibition of T-cell activation |
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| Authors: | W Holter O Majdic H Stockinger K Liszka G Fischer W Knapp |
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| Institution: | 1. Xinjiang Key Laboratory for Luminescence Minerals and Optical Functional Materials, School of Physics and Electronic Engineering, Xinjiang Normal University, Urumqi, Xinjiang 830054, China;2. Laboratory and Equipment Management Division, Xinjiang Normal University, Urumqi, Xinjiang 830054, China;1. Reproductive Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;2. Guangzhou Baiyunshan Zhongyi Pharmaceutical Co. Ltd, Guangzhou, Guangdong, 510530, China;1. The University of Arizona College of Medicine – Phoenix, Creighton University School of Medicine-Phoenix, Valleywise Health Medical Center, 2601 E Roosevelt St, Phoenix, AZ, 85008, USA;2. Department of Psychiatry, Valleywise Health Medical Center, Creighton University School of Medicine, 2601 E Roosevelt St, Phoenix, AZ, USA;3. Creighton University School of Medicine, Class of 2022, Phoenix, AZ, USA;4. Distinguished Career Professor of Psychiatry (Adjunct Faculty), Virginia Commonwealth University, Richmond, VA, United States;5. Clinical Research Coordinator II, Department of Research, Valleywise Health 2601 E Roosevelt St, Phoenix, AZ, 85008, USA;6. Department of Research, Valleywise Health, 2601 E Roosevelt St, Phoenix, AZ, 85008, USA;7. Psychiatry Department, Valleywise Health System, Academic Chair, Creighton University School of Medicine, Phoenix Regional Campus, Psychiatry Division, District Medical Group, Phoenix, AZ, USA |
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| Abstract: | In this study the influence of a non-mitogenic anti-CD3 antibody on accessory cell-dependent antigen and mitogen-induced T-lymphocyte proliferation has been investigated. The antibody was found to completely inhibit PHA, Con A, PWM, and tetanus toxoid stimulation, with no effect on the proliferation induced by the calcium ionophore A23187. VIT3 completely abrogated the production of IL-2 by lectin-stimulated T cells. It had no effect, however, on the IL-2-dependent proliferation of preactivated T-cell blasts. In addition, the antibody was able to elevate free cytoplasmic Ca2+ levels within minutes after the addition to T cells. Detailed time kinetic analyses revealed that the time interval critical for inhibition was significantly dependent on the interaction between T cells and accessory cells. Under standard conditions, in the presence of 10% non-T cells as accessory cells 50% inhibition was still achieved when VIT3 was added to PHA-stimulated T cells as late as 8 hr after the onset of culture. Delayed addition or a decrease in the number of added accessory cells significantly prolonged this time period. Lectin-stimulated T cells can thus obviously be inhibited via CD3 as long as they have not received all signals including those delivered by accessory cells. Although the underlying mechanisms are not clear so far, the observation that VIT3 at the same time triggers an early cytoplasmic Ca2+ response might indicate that it thereby actively interferes with antigen and lectin-initiated activation processes. |
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