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在完全异种(大鼠→小鼠)嵌合体和同基因重建(A→A)大鼠的淋巴细胞上NKR-P1与αβ-TCR的共表达。

Coexpression of NKR-P1 and alpha beta-TCR on lymphoid cells in fully xenogeneic (rat-->mouse) chimeras and syngeneically reconstituted (A-->A) rats.

作者信息

Kaufman C L, Chambers W H, Ildstad S T

机构信息

Department of Surgery, University of Pittsburgh, PA 15261.

出版信息

J Immunol. 1993 Dec 1;151(11):6002-11.

PMID:8245445
Abstract

We have identified three populations of cells among rat splenocytes expressing NKR-P1, including cells of NKR-P1bright/alpha beta-TCR-, NKR-P1dim/alpha beta-TCR+, and NKR-P1dim/alpha beta-TCR- phenotypes. To study the phenotypic characteristics and development of these various cell populations, we have made use of transplanting untreated rat bone marrow into recipient rats (syngeneic) or mice (fully xenogeneic) conditioned with total body irradiation. Rat NK cells exhibit normal phenotypic markers (NKR-P1+, CD8+) and are normally functional by 28 days after reconstitution. We have found that the various populations of NKR-P1+ cells are enriched significantly in the spleen and follow a characteristic pattern of development in the first mo after reconstitution. After syngeneic bone marrow reconstitution (rat-->rat), NKR-P1dim and NKR-P1bright cells (3-15%) can be demonstrated among splenocytes as early as day 3 after bone marrow transplantation. By day 7, the NKR-P1+ cells reach peak levels and comprise as much as 80% of splenic lymphoid cells, with 35% being NKR-P1bright and 45% being NKR-P1dim. The percentage of NKR-P1+ cells decreases over the next several wk until they constitute "normal rat" levels with 8 to 20% being NKR-P1bright and only 1 to 5% being NKR-P1dim. These same populations are also present in fully xenogeneic chimeras. In both models, approximately 80 to 90% of the NKR-P1dim cells were found to coexpress alpha beta-TCR at all time points. These NKR-P1dim/alpha beta-TCR+ cells are not large granular lymphocytes and lack NK cell lytic activity against YAC-1 target cells. Additional analyses of cells derived from spleen, bone marrow, and thymus indicated that NKR-P1+ cells develop, for the most part, in a thymic-independent manner in our fully xenogeneic chimeras and syngeneically reconstituted rats. At present the developmental pathway of these NKR-P1dim cells remains speculative.

摘要

我们在表达NKR-P1的大鼠脾细胞中鉴定出三类细胞群体,包括NKR-P1bright/αβ-TCR-、NKR-P1dim/αβ-TCR+和NKR-P1dim/αβ-TCR-表型的细胞。为了研究这些不同细胞群体的表型特征和发育情况,我们将未经处理的大鼠骨髓移植到经全身照射预处理的受体大鼠(同基因)或小鼠(完全异种基因)体内。大鼠自然杀伤(NK)细胞表现出正常的表型标志物(NKR-P1+、CD8+),并且在重建后28天功能正常。我们发现,NKR-P1+细胞的不同群体在脾脏中显著富集,并在重建后的第一个月遵循特征性的发育模式。在同基因骨髓重建(大鼠→大鼠)后,早在骨髓移植后第3天,脾细胞中就可检测到NKR-P1dim和NKR-P1bright细胞(3%-15%)。到第7天,NKR-P1+细胞达到峰值水平,占脾淋巴细胞的80%之多,其中35%为NKR-P1bright,45%为NKR-P1dim。在接下来的几周内,NKR-P1+细胞的百分比下降,直至达到“正常大鼠”水平,其中8%-20%为NKR-P1bright,仅1%-5%为NKR-P1dim。这些相同的细胞群体也存在于完全异种基因嵌合体中。在这两种模型中,在所有时间点均发现约80%-90%的NKR-P1dim细胞共表达αβ-TCR。这些NKR-P1dim/αβ-TCR+细胞不是大颗粒淋巴细胞,并且缺乏针对YAC-1靶细胞的NK细胞裂解活性。对来自脾脏、骨髓和胸腺的细胞进行的进一步分析表明,在我们的完全异种基因嵌合体和同基因重建大鼠中,NKR-P1+细胞在很大程度上以不依赖胸腺的方式发育。目前,这些NKR-P1dim细胞的发育途径仍具有推测性。

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