在β2-微球蛋白、MHC I类缺陷小鼠中具有高度溶解性的CD8 +、αβT细胞受体细胞毒性T细胞，其具有针对主要组织相容性复合体（MHC）I类抗原的细胞毒性。
Highly lytic CD8+, alpha beta T-cell receptor cytotoxic T cells with major histocompatibility complex (MHC) class I antigen-directed cytotoxicity in beta 2-microglobulin, MHC class I-deficient mice.
作者信息
Apasov S, Sitkovsky M
机构信息
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
出版信息
Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2837-41. doi: 10.1073/pnas.90.7.2837.
Abstract
Targeted disruption of the beta 2-microglobulin (beta 2m) gene results in major histocompatibility complex (MHC) class I deficiency and virtual disappearance of functional CD8+ cytotoxic T lymphocytes (CTLs) in beta 2m-deficient (beta 2m-/-) mice. We asked whether the beta 2m-/- mice are able to reject tumor cells injected i.p. and what is the cellular composition of peritoneal exudate leukocytes (PELs) from such mice. We found that beta 2m-/- mice do reject MHC class I-bearing tumor cells injected i.p. Surprisingly, analysis of PEL CTLs obtained from i.p. tumor-injected beta 2m -/- mice revealed the presence of a large proportion of functional, tumor-destroying CD8+, CD4-, alpha beta T-cell receptor-positive, CD3+, Thy-1+, MHC class I-negative CTLs with strong MHC class I-directed cytotoxic activity. These results call for careful studies of local accumulation of CD8+ CTLs in beta 2m -/- mouse models and suggest that the dramatic decrease in MHC class I expression caused by beta 2m gene disruption does not prevent CD8+/CD4- cell selection and expansion.
摘要
β2微球蛋白（β2m）基因的靶向破坏导致主要组织相容性复合体（MHC）I类缺陷，且β2m缺陷（β2m-/-）小鼠体内功能性CD8+细胞毒性T淋巴细胞（CTL）几乎消失。我们探究了β2m-/-小鼠是否能够排斥腹腔注射的肿瘤细胞，以及此类小鼠腹腔渗出液白细胞（PEL）的细胞组成情况。我们发现β2m-/-小鼠确实能够排斥腹腔注射的携带MHC I类的肿瘤细胞。令人惊讶的是，对腹腔注射肿瘤的β2m-/-小鼠的PEL CTL分析显示，存在很大比例具有功能、可破坏肿瘤的CD8+、CD4-、αβT细胞受体阳性、CD3+、Thy-1+、MHC I类阴性的CTL，它们具有很强的MHC I类定向细胞毒性活性。这些结果要求对β2m-/-小鼠模型中CD8+ CTL的局部聚集进行仔细研究，并表明β2m基因破坏导致的MHC I类表达显著降低并不妨碍CD8+/CD4-细胞的选择和扩增。
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本文引用的文献
1
HLA-A locus alleles identified by sequence specific PCR.通过序列特异性PCR鉴定的HLA - A基因座等位基因。
Lancet. 1993 Jan 9;341(8837):121-2. doi: 10.1016/0140-6736(93)92605-s.
2
Distribution of HLA class 1 antigens in normal human tissue and in mammary cancer.人类主要组织相容性复合体I类抗原在正常人体组织及乳腺癌组织中的分布
J Clin Pathol. 1981 Jul;34(7):779-84. doi: 10.1136/jcp.34.7.779.
3
Hormonal control of human colon carcinoma cell growth in serum-free medium.无血清培养基中人类结肠癌细胞生长的激素调控
Proc Natl Acad Sci U S A. 1980 Jun;77(6):3464-8. doi: 10.1073/pnas.77.6.3464.
4
The isolation and characterization of colorectal epithelial cell lines at different stages in malignant transformation from familial polyposis coli patients.从家族性结肠息肉病患者中分离并鉴定处于恶性转化不同阶段的结肠上皮细胞系。
Int J Cancer. 1984 Jul 15;34(1):49-56. doi: 10.1002/ijc.2910340109.
5
Protection against two spontaneous mouse leukemias conferred by immunogenic variants obtained by mutagenesis.通过诱变获得的免疫原性变体对两种自发性小鼠白血病的保护作用。
J Exp Med. 1983 Jun 1;157(6):1992-2001. doi: 10.1084/jem.157.6.1992.
6
Establishment and characterization of human colorectal cancer cell lines.人结肠癌细胞系的建立与鉴定
Cancer Res. 1984 Dec;44(12 Pt 1):5813-21.
7
Expression of major histocompatibility antigens and nature of inflammatory cellular infiltrate in ovarian neoplasms.卵巢肿瘤中主要组织相容性抗原的表达及炎性细胞浸润的性质
Int J Cancer. 1983 Nov 15;32(5):547-54. doi: 10.1002/ijc.2910320505.
8
Striking paucity of HLA-A, B, C and beta 2-microglobulin on human neuroblastoma cell lines.人类神经母细胞瘤细胞系中HLA - A、B、C及β2 -微球蛋白明显缺乏。
J Immunol. 1983 May;130(5):2471-8.
9
Rejection of ascites tumor allografts. II. A pathway for cell-mediated tumor destruction in vitro by peritoneal exudate lymphoid cells.腹水肿瘤同种异体移植的排斥反应。II. 腹膜渗出液淋巴细胞在体外介导细胞性肿瘤破坏的途径。
J Exp Med. 1972 Dec 1;136(6):1594-604. doi: 10.1084/jem.136.6.1594.
10
Cytotoxic lymphocytes in the absence of detectable antibody.在无可检测抗体情况下的细胞毒性淋巴细胞。
Nat New Biol. 1973 Apr 25;242(121):237-9. doi: 10.1038/newbio242237a0.
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