Transient accumulation of human mature thymocytes and regulatory T cells with CD28 superagonist in 'human immune system' Rag2(-/-)gammac(-/-) mice
| Autor: | Hergen Spits, Nicolas Legrand, Anja U. van Lent, Thomas Hanke, Tom Cupedo, Kees Weijer, Menno J. Ebeli |
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| Přispěvatelé: | Other departments, Amsterdam institute for Infection and Immunity, Cell Biology and Histology, Amsterdam Gastroenterology Endocrinology Metabolism |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_treatment
T-Lymphocytes Immunology Mice Transgenic chemical and pharmacologic phenomena Thymus Gland Biology Biochemistry T-Lymphocytes Regulatory Mice Structure-Activity Relationship Immune system CD28 Antigens medicine Animals Humans IL-2 receptor Mice Knockout Mice Inbred BALB C T-cell receptor CD28 FOXP3 Antibodies Monoclonal Cell Differentiation Cell Biology Hematology T lymphocyte Immunotherapy Cell biology DNA-Binding Proteins Thymocyte Disease Models Animal |
| Zdroj: | Blood, 108(1), 238-245. American Society of Hematology |
| ISSN: | 0006-4971 |
| Popis: | Efficient and quick reconstitution of T-cell compartments in lymphopenic patients is of great importance to prevent opportunistic infections, but remains difficult to achieve. Human T-cell proliferation in a T-cell-receptor (TCR)-independent manner is possible in vitro with superagonist anti-CD28 antibodies, and such molecules are therefore promising therapeutic tools. Here, we investigated the in vivo effects of superagonist anti-CD28 treatment on human developing and mature T cells, in the recently developed model of “human immune system” BALB/c Rag2-/-γc-/- mice. Our results show that superagonist anti-CD28 treatment transiently induces a 7-fold increase in thymocyte numbers and up to 18-fold accumulation of mature thymocytes. The increased thymic production lead to transient accumulation of mature T cells in the periphery at the peak of treatment effect (day 6). In addition, long-term peripheral T-cell depletion was induced. Furthermore, the concomitant selective expansion and accumulation of suppressive CD4+CD25+FoxP3+ T cells was induced in a transient manner. Superagonist anti-CD28 therapy could therefore be of clinical interest in humans, both for beneficial effect on thymic T-cell production as well as regulatory T-cell accumulation. (Blood. 2006;108:238-245) |
| Databáze: | OpenAIRE |
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