ST8Sia6 deficiency is insufficient to induce complement-mediated attack on recent thymic emigrants
| Autor: | Paul Belmonte, Fan-Chi Hsu, Barsha Dash, Ji Young Chung, Sinibaldo Romero Arocha, Virginia Shapiro |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 198:60.17-60.17 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | T cells require additional developmental steps after positive selection before they are functionally competent and can enter the long-lived peripheral T cell pool. During maturation, T cells gain the ability to produce cytokines upon stimulation, and the ability to protect themselves from TNF and complement-mediated cell death. In three different mouse models with defects in T cell maturation (CD4-cre NKAP conditional knockout mice, CD4-cre HDAC3 conditional knockout mice and CD4-cre RUNX1 conditional knockout mice), recent thymic emigrant (RTE) numbers are greatly reduced due to complement-mediated attack initiated by the binding of IgM and activation of the classical pathway. These models have deficiencies in the addition of sialic acid modifications, which is normally increased during the later stages of T cell development. As stripping cell surface sialic acids by neuraminidase on peripheral T cells leads to binding of natural IgM and complement activation, it was hypothesized complement-mediated attack is due to a defect in sialylation. Transcriptionally, the sialic acid transferase ST8Sia6 is upregulated concurrently with T cell maturation after positive selection. To understand the role of ST8Sia6 in T cell maturation, we generated ST8Sia6 knockout mice. These mice are healthy and fertile. RTEs and mature T cells are present in the periphery in normal numbers, and do not show evidence of complement deposition. Therefore, loss of ST8Sia6 alone is insufficient to induce complement-mediated attack on RTEs and other co-expressed sialyltransferases may also be required to protect from complement deposition. |
| Databáze: | OpenAIRE |
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