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2014 ; 193
(12
): 6005-15
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Immature recent thymic emigrants are eliminated by complement
#MMPMID25367120
Hsu FC
; Shapiro MJ
; Chen MW
; McWilliams DC
; Seaburg LM
; Tangen SN
; Shapiro VS
J Immunol
2014[Dec]; 193
(12
): 6005-15
PMID25367120
show ga
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 ?2,8-linked
sialylation, and the expression of three genes (ST8sia1, ST8sia4, and ST8sia6)
that mediate ?2,8 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.
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