B and T lymphocyte attenuator exhibits structural and expression polymorphisms and is highly induced in anergic CD4+ T cells
B and T lymphocyte attenuator exhibits structural and expression polymorphisms and is highly induced in anergic CD4+ T cells
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DOI：
10.4049/jimmunol.174.6.3377
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发表时间：
2005-03-15
影响因子：
4.4
通讯作者：
Murphy, KM
中科院分区：
文献类型：
--
作者：
Hurchla, MA;Sedy, JR;Murphy, KM
B和T淋巴细胞衰减剂（BTLA）最初被鉴定为在Th1细胞和B细胞上表达的，但最近据报道，巨噬细胞，树突细胞和NK细胞也表达。为了解决这一差异，我们生成了一组BTLA特异性mAb，并在各种激活条件下表征了BTLA表达。我们报告了23个鼠菌株中存在三个不同的BTLA等位基因，在Ig结构域结构和淋巴样子集表达的细胞分布之间存在不同。 BALB/C和MRL/LPR等位基因在一个氨基酸残基上有所不同，但是C57BL/6具有9个其他差异，并改变了预测的半胱氨酸键合模式。 BALB/C BTLA等位基因也由B细胞，T细胞和树突状细胞表达，而不是巨噬细胞或NK细胞。但是，C57BL/6 BTLA在CD11b（+）巨噬细胞和NK细胞上表达。最后，在CD4（+）T细胞中，BTLA在体内的Ag特异性诱导后表达了最高的表达，并且与编程的Death-1和CTLA-4不同，CD25（+）调节性T细胞未表达。这些结果阐明了有关BTLA表达的差异，表明在分析各种鼠背景的BTLA时，考虑结构和表达多态性，并表明在厌氧CD4（+）T细胞中可能起作用。
B and T lymphocyte attenuator (BTLA) was initially identified as expressed on Th1 cells and B cells, but recently reported to be expressed by macrophages, dendritie cells, and NK cells as well. To address this discrepancy we generated a panel of BTLA-specific mAbs and characterized BTLA expression under various activation conditions. We report the existence of three distinct BTLA alleles among 23 murine strains, differing both in Ig domain structure and cellular distribution of expression on lymphoid subsets. The BALB/c and MRL/lpr alleles differ at one amino acid residue, but C57BL/6 has nine additional differences and alters the predicted cysteine bonding pattern. The BALB/c BTLA allele is also expressed by B cells, T cells, and dendritic cells, but not macrophages or NK cells. However, C57BL/6 BTLA is expressed on CD11b(+) macrophages and NK cells. Finally, in CD4(+) T cells, BTLA is expressed most highly following Ag-specific induction of anergy in vivo, and unlike programmed death-1 and CTLA-4, not expressed by CD25(+) regulatory T cells. These results clarify discrepancies regarding BTLA expression, suggest that structural and expression polymorphisms be considered when analyzing BTLA in various murine backgrounds, and indicate a possible role in anergic CD4(+) T cells.