Negative selection of lymphocytes

Nossal, G. J. V.

doi:10.1016/0092-8674(94)90331-x

Cited by 727 publications

(399 citation statements)

References 49 publications

Supporting

Mentioning

388

Contrasting

Unclassified

Order By: Relevance

“…Despite Siva-1 lacking the typical death and Bcl-2 homology (BH) domains, it appears to promote both intrinsic and extrinsic cell death pathways (Henke et al, 2000;Cao et al, 2001;Spinicelli et al, 2002;Chu et al, 2004Chu et al, , 2005. Expression of Siva-1 is restricted to doublepositive thymocytes (Xue et al, 2002), the majority of which are known to undergo negative selection (Nossal, 1994) and also in highly activated peripheral T cells targeted for AICD (supplement 1) thereby indicating a role for Siva-1 in TCR-mediated AICD.…”

mentioning

confidence: 99%

Siva-1 negatively regulates NF-κB activity: effect on T-cell receptor-mediated activation-induced cell death (AICD)

et al. 2006

View full text Add to dashboard Cite

mentioning

confidence: 99%

Siva-1 negatively regulates NF-κB activity: effect on T-cell receptor-mediated activation-induced cell death (AICD)

et al. 2006

View full text Add to dashboard Cite

“…Thymic stromal cells, including epithelial cells, macrophages and dendritic cells, are thought to play a role in positive and negative selection. Thymic stromal cells express high levels of class I and class II MHC molecules allowing immature thymocytes expressing the TcR-CD3 complex to interact, leading to positive and negative selection (1,(4)(5)(6).…”

mentioning

confidence: 99%

“…Interaction of immature CD4 þ 8 þ thymocytes bearing receptors capable of binding self-MHC molecules, with thymic epithelial cells survive as they may receive a protective signal on binding. Those cells whose receptors are not MHC restricted do not interact with thymic epithelial cells and consequently do not receive the protective signal, thus leading to their death within 3-4 days via apoptosis (1,(4)(5)(6).…”

mentioning

confidence: 99%

“…During negative selection, dendritic cells and macrophages bearing class I and class II MHC molecules are thought to interact with thymocytes bearing high affinity receptors for self-antigen plus self-MHC molecules, or self-MHC molecules alone. The nature of the interaction is unknown, but the selected cells undergo death by apoptosis (1,3,5). Apoptotic selection of specific clones of thymocytes is not single mechanisms of thymic tolerance induction.…”

mentioning

confidence: 99%

“…All cells in the thymus express MHC class I molecules but the highest expression is on nonepithelial cells. Although self/nonself 'education' and acquisition of haplotype restriction of developing T cells requires intrathymic expressed MHC molecules (1,3,6).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Induction of thymic tolerance as possibility in prevention of recurrent spontaneous abortion

Bubanovic¹

2003

Medical Hypotheses

View full text Add to dashboard Cite

Summary A major process through which the immune system becomes tolerant to self-proteins involves the deletion of self-reactive cells in the thymus and/or inhibition of specific Th 1 cells clones. Deletion process includes two selection mechanisms in which the thymus eliminates unwanted thymocytes are known as positive selection and negative selection. The thymus is an antigenically privileged site, mainly for it is discrete by blood-thymus barrier. Many researches were shown that intrathymic inoculation of any antigen resulted in specific tolerance induction. The embryo/fetus and placenta are an allograft to which the mother must remain immunologically tolerant in order for the fetus to survive. Today, there is much interest focused on the immunology of recurrent spontaneous abortion (RSA). Up to 50% of RSA may be mediated by the immune system via inadequate maternal anti-paternal response. Nature of this maternal-fetal disturbance represents disbalance in Th 1 =Th 2 activity. Contra-shift in Th 1 =Th 2 activity is the basis for immunotherapy with paternal leukocyte immunization (PLI). PLI induce some kind of peripheral tolerance on embryonic/fetal/trophoblast antigens, but problems of central tolerance are still open. Intrathymic inoculation of fetal or paternal cells (like leukocyte, thymic dendritic cells, trophoblast cells) or paternal set of MHC molecules may cause central specific tolerance and may be a new possibility for immunotherapy in RSA patients. ª

show abstract

Alterations of the thymic selection process in transgenic mice expressing SV40 large T antigen

Lee¹,

Seo

1996

Int. J. Cancer

View full text Add to dashboard Cite

We generated SV40 T antigen transgenic mice (lines SVTl25, SVT 127, and SVT248) which developed unique thymic carcinomas originating from thymic cortical epithelial cells. In these mice we observed alterations in the thymic selection process Thymic stromal cells constituting the thymic microenvironment play critical roles in the induction of T cell maturation and selection events in the thymus. The precursors of T lymphocytes originate in the bone marrow (or fetal liver) and migrate to the thymus. In the thymic microenvironment these cells then proliferate and begin T cell receptor (TCR) gene rearrangement. During the thymic selection process, precursor T cells, originally CD4-CD8-TCR-, go through a CD4+CD8+TCRtow stage and finally mature into either CD4-CD8+TCRhlgh or CD4+CD8-TCRh1@' T cells that recognize antigenic peptides associated with MHC class-I or -11 molecules, respectively (reviewed by Weissman, 1994). Since TCR gene rearrangement is a random event, a selection process is required to eliminate potentially harmful selfreactive T cells and to allow development of T cells with proper TCRs. Thymocytes with excessive self-reactivity undergo a clonal deletion process (negative selection) which is mediated by apoptosis (programmed cell death). Negative selection occurs at the CD4+CD8+TCR+ stage. Thymocytes with sufficient but not high reactivity for self-MHC molecules are allowed to mature into functional T cells (positive selection). The differentiation of the 2 major subsets of T cells also depends on the specificity of the TCR: engagement of TCRs with either MHC class-I or class-I1 molecules causes the T cells to mature into either CD8+ CTLs or CD4+ helper T cells, respectively (reviewed by Nossal, 1994;von Boehmer, 1994).A variety of cell types, including thymic nurse cells, cortical epithelial cells, medullary epithelial cells, dendritic cells and macrophages, comprise the thymic stroma (reviewed by Boyd et al., 1993). These cells are believed to provide plasma membrane intercellular communication molecules and the local gradients of specific cytokines that direct the discrete phases of T cell development. Furthermore, thymic stromal cells and thymocytes are in a symbiotic developmental relationship, sharing the expression of many cytokines and cytokine receptors (reviewed by Ritter and Boyd, 1993).A major pathology observed in transgenic mice harboring the SV40 T antigen is brain tumor. Minor lesions in the thymus and kidney are also observed (Brinster et aZ., 1984; Pinkert et al., 1087;van Dyke et al., 1987). With the use of various types of promoters, abnormalities of other types were developed in other organs, for example tumor in pancreatic p-cells (Hanahan, 1985), lymphoma, and adenocarcinoma (Choi et al., 1987; Wikenheiser et al., 1992). Thymic hyperplasia was also observed in transgenic mice expressing SV40 T antigen under the control of its own promoter (Palmiter et al., 1985) or human growth-hormone-releasing-factor gene promoter (Botteri et al., 1987;Moll et al., 1992).We generated transge...

show abstract

Negative selection of lymphocytes

Cited by 727 publications

References 49 publications

Siva-1 negatively regulates NF-κB activity: effect on T-cell receptor-mediated activation-induced cell death (AICD)

Siva-1 negatively regulates NF-κB activity: effect on T-cell receptor-mediated activation-induced cell death (AICD)

Induction of thymic tolerance as possibility in prevention of recurrent spontaneous abortion

Alterations of the thymic selection process in transgenic mice expressing SV40 large T antigen

Contact Info

Product

Resources

About