ISSN:0883-0185    

DOI:10.3109/08830189409061713

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Recent studies of the TCRαandβchains expressed by normal human IELs suggest that these intestinal lymphocytes are directed at a limited set of antigens, presumably on intestinal epithelial cells in view of their anatomic location. The direct sequence analysis of these cells has indicated that they are oligoclonal and cannot, therefore, be responding to the complex mixture of antigens which are present in the lumen. The abundant expression of the CD8 accessory molecule by the IELs, in addition, indicates that these putative intestinal epithelial cell antigens are presented by MHC class I or I-like molecules. The expression of CD8 also suggests that these cells function biologically in part as cytolytic T lymphocytes which is consistent with a variety of functional studies. Taken together with their expression of the CD45RO isoform, these phenotypic and functional observations suggest that iIELs are cytolytic, memory cells which are responsive to an extremely limited number of antigens bound to major histocompatibility complex (MHC) class I or class I-like molecules. Several non-polymorphic MHC class I-like molecules such as Qa, the thymus leukemia antigen (TL) and CD1 in the mouse and CD1 in humans represent important candidate ligands for these oligoclonal iIELs. TL and CD1 are expressed specifically by murine intestinal epithelial cells. In humans, CDld is constitutively expressed by intestinal epithelial cells. In addition, we have isolated iIEL T cell clones which specifically recognize members of the CD1 gene family when expressed on a transfected B cell line that lacks HLA-A and B and have shown that the proliferation of peripheral blood T cells to intestinal epithelial cells is CDld dependent. Thus, the evidence to date strongly implicate the nonpolymorphic, class lb molecules as novel restriction elements for unique populations of lymphocytes within the intestinal epithelium.

ISSN:0883-0185    

DOI:10.3109/08830189409061714

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We found that a homogenous CD4-/CD8- T cell bearing an invariant TCR encoded by Vα14Jα281 with a one-base N-region is highly dominant in the periphery (2-3% in spleen). Surprisingly, the high expression of this invariant Vα14 TCR is a general phenomenon in all laboratory strains irrespective of MHC haplotype and in some wild mouse subspecies. The majority of Vα14+ TCR is associated with Jαother than Jα281 during the neonatal stage, after which the frequency of invariant Vα14Jα281 TCR expression increases with time reaching a maximum at around 5-8 weeks after birth. The dominant expression of Vα14Jα281 TCR is found in both euthymic and athymic mice. These results indicate that homogenous Vα14Jα281 T cells are positively selected in the periphery without thymic influence and that their VJ junction is important for positive selection. We also demonstrate that Vα14+TCR gene rearrangements take place at extrathymic sites, such as bone marrow, liver, and intestine, since frequent nonproductive Vα14 TCR products and Vα14-Jα281 gene mediated signal sequences in circular DNA are detected as a result of TCR rearrangements in extrathymic tissues rather than in the thymus. This indicates the extrathymic development of Vα14Jα281 T cells. Furthermore, the biological roles of homogenous T cells bearing Vα14Jα281 TCR and the human counterpart of this invariant TCR are also discussed.

ISSN:0883-0185    

DOI:10.3109/08830189409061715

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Intestinal intraepithelial lymphocytes (i-IEL) are phenotypically diverse and consist of both thymically derived and extrathymically derived cells. Extrathymically derived i-IEL are clearly different from thymically derived peripheral T cells in their phenotype and repertoire selection. The major locus of differentiation of extrathymically derived i-IEL appears to be the intestinal epithelium because recombination activating gene (RAG)-1 is expressed in CD3−i-IEL. Extrathymic differentiation however does not imply independence from the thymus as athymic mice have increased numbers of CD3−CD8−and CD3−CD8αα+i-IEL but decreased numbers of CD3+CD8αα+i-IEL when compared to euthymic mice. We speculate from these results that thymus-derived cytokine(s)/factor(s) may support differentiation from CD3−CD8αα+to CD3+CD8αα+i-IEL in the intestinal epithelium.I-IEL seem to have some role in immune surveillance because they reside at a site which may represent a first line of defense against pathogenic organisms. This idea is supported by the reports showingin vivoactivation of i-IEL under conditions of intestinal infection or tumor-bearing state.In vitroanalyses showed cytotoxicity and cytokine production of i-IEL but their true function(s)in vivois(are) not well known. Clearly more analysis on thein vivofunction(s) of i-IEL are needed in order to clarify the true role(s) of i-IEL.

ISSN:0883-0185    

DOI:10.3109/08830189409061716

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189409061717

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0883-0185    

DOI:10.3109/08830189409061712

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor