Immature recent thymic emigrants are eliminated by complement

Fan Chi Hsu, Michael J. Shapiro, Meibo W. Chen, Douglas C. McWilliams, Lauren M. Seaburg, Sarah N. Tangen, Virginia M Shapiro

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Recent thymic emigrants (RTEs) must undergo phenotypic and functional maturation to become long-lived mature naive T cells. In CD4-cre NKAP conditional knockout mice, NKAP-deficient RTEs fail to complete T cell maturation. In this study, we demonstrate that NKAP-deficient immature RTEs do not undergo apoptosis, but are eliminated by complement. C3, C4, and C1q are bound to NKAP-deficient peripheral T cells, demonstrating activation of the classical arm of the complement pathway. As thymocytes mature and exit to the periphery, they increase sialic acid incorporation into cell surface glycans. This is essential to peripheral lymphocyte survival, as stripping sialic acid with neuraminidase leads to the binding of natural IgM and complement fixation. NKAP-deficient T cells have a defect in sialylation on cell surface glycans, leading to IgM recruitment. We demonstrate that the defect in sialylation is due to aberrant α2,8-linked sialylation, and the expression of three genes (ST8sia1, ST8sia4, and ST8sia6) that mediate α2,8 sialylation are downregulated in NKAP-defcient RTEs. The maturation of peripheral NKAP-deficient T cells is partially rescued in a C3-deficient environment. Thus, sialylation during T cell maturation is critical to protect immature RTEs from complement in the periphery.

Original languageEnglish (US)
Pages (from-to)6005-6015
Number of pages11
JournalJournal of Immunology
Volume193
Issue number12
DOIs
StatePublished - Dec 15 2014

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T-Lymphocytes
N-Acetylneuraminic Acid
Polysaccharides
Immunoglobulin M
Classical Complement Pathway
Neuraminidase
Thymocytes
Knockout Mice
Down-Regulation
Lymphocytes
Apoptosis
Gene Expression

ASJC Scopus subject areas

  • Immunology

Cite this

Hsu, F. C., Shapiro, M. J., Chen, M. W., McWilliams, D. C., Seaburg, L. M., Tangen, S. N., & Shapiro, V. M. (2014). Immature recent thymic emigrants are eliminated by complement. Journal of Immunology, 193(12), 6005-6015. https://doi.org/10.4049/jimmunol.1401871

Immature recent thymic emigrants are eliminated by complement. / Hsu, Fan Chi; Shapiro, Michael J.; Chen, Meibo W.; McWilliams, Douglas C.; Seaburg, Lauren M.; Tangen, Sarah N.; Shapiro, Virginia M.

In: Journal of Immunology, Vol. 193, No. 12, 15.12.2014, p. 6005-6015.

Research output: Contribution to journalArticle

Hsu, FC, Shapiro, MJ, Chen, MW, McWilliams, DC, Seaburg, LM, Tangen, SN & Shapiro, VM 2014, 'Immature recent thymic emigrants are eliminated by complement', Journal of Immunology, vol. 193, no. 12, pp. 6005-6015. https://doi.org/10.4049/jimmunol.1401871
Hsu FC, Shapiro MJ, Chen MW, McWilliams DC, Seaburg LM, Tangen SN et al. Immature recent thymic emigrants are eliminated by complement. Journal of Immunology. 2014 Dec 15;193(12):6005-6015. https://doi.org/10.4049/jimmunol.1401871
Hsu, Fan Chi ; Shapiro, Michael J. ; Chen, Meibo W. ; McWilliams, Douglas C. ; Seaburg, Lauren M. ; Tangen, Sarah N. ; Shapiro, Virginia M. / Immature recent thymic emigrants are eliminated by complement. In: Journal of Immunology. 2014 ; Vol. 193, No. 12. pp. 6005-6015.
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