PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11975804

Why do we reject grafts?

C B Carpenter
View original source ↗Export metadata ↓

Abstract

One of the puzzles in clinical and experimental organ and tissue transplantation has been why it is that, with the exception of transplantation between genetically identical twin pairs, transplantation results in a rapidly progressing immune response to the point of tissue necrosis in a matter of a few days, even though the recipient has not been immunized to the donor. Indeed, the numbers of T lymphocytes predetermined to react against grafts are relatively abundant compared to those that recognize microbial antigens. Cellular, molecular, and genetic studies are now revealing the nature of T-cell recognition, and why it is that we cannot freely exchange tissue grafts.

Explore related subjects

Antigen-Presenting CellsGraft RejectionHumansMajor Histocompatibility ComplexT-LymphocytesTransplantation ImmunologyJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

C B Carpenter. Why do we reject grafts?. https://doi.org/10.1097/00132580-200107000-00010

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

CD2 and TCR synergize for the activation of phospholipase Cgamma1/calcium pathway at the immunological synapse.

Upon conjugation with cognate antigen-presenting cells (APCs), T lymphocytes undergo a sustained [Ca(2+)](i) increase resulting from the engagement of TCR and of accessory molecules with ligands expressed on the surface of APCs. We investigated the contribution of the accessory molecule CD2 to the activation of phospholipase Cgamma1 (PLCgamma1)/calcium pathway in antigen-stimulated T cells. We show that CD2 binding with its ligand CD58 expressed on the surface of APCs augments and sustains antigen-induced [Ca(2+)](i) increase in individual T cells interacting with APCs. We also show that in conditions in which CD2-CD58 interaction is impeded, the recruitment of PLCgamma1 to the immunological synapse (IS) is reduced. Interestingly, in these conditions PLCgamma1 phosphorylation in the regulatory tyrosine 783 is also defective. Our results indicate that TCR- and CD2-derived signals converge for the recruitment and activation of PLCgamma1 at the IS and shed new light on the accessory function of CD2 in T cell activation by specific antigen.

Antigen-Presenting Cells↗
PubMed2007

Langhans giant cells from M. tuberculosis-induced human granulomas cannot mediate mycobacterial uptake.

Tuberculosis is characterized by a tight interplay between Mycobacterium tuberculosis (M. tb) and host cells within granulomas. These cellular aggregates restrain M. tb spreading but do not kill all bacilli, which persist for years. A more detailed investigation of the interaction between M. tb and granuloma cells is needed to improve our understanding of this persistence and to explain the physiopathology of tuberculosis. In the present study, a recently developed in vitro human model of tuberculous granulomas has been used to analyse the modulation of granuloma cell differentiation by M. tb, in comparison to poorly virulent mycobacteria, which do not persist. It is reported that whilst all mycobacteria species induce granuloma formation, only M. tb triggers the differentiation of granuloma macrophages into very large multinucleated giant cells (MGCs) that are unable to mediate any bacterial uptake. This loss of function is not due to cell quiescence, as MGCs still display NADPH oxidase activity, but it correlates with decreased expression of phagocytosis receptors. This phenomenon is specific for the virulent species of M. tuberculosis complex, as poorly virulent species only induce the formation of small multinucleated cells (MCs) with conserved mycobacterial uptake ability, which never reach the MGC differentiation stage. The phenotype of MGCs thus strongly resembles mature dendritic cells with a loss of microbial uptake ability, despite conserved antigen presentation. In M. tb-induced granulomas, MGCs thus seem to be devoted to the destruction of bacilli that have been ingested in previous differentiation stages, ie in macrophages and MCs.

Antigen-Presenting Cells↗
PubMed2007

Immunopathogenesis of Behçet's disease with special emphasize on the possible role of antigen presenting cells.

Behçet's disease (BD) is a systemic vasculitis with unclear etiology and pathogenesis. Although several viral and bacterial causes have been investigated in detail for several years, of late it is widely accepted that microorganisms may play a role as a trigger, or as a cross-reactive antigens that interfere with self-antigens, such as heat-shock proteins. Genes such as HLA-B51, MICA and TNF, considered to play a crucial role in the pathogenesis of BD, are located in the major histocompatibility complex (MHC). However, it has been accepted that, only HLA-B51 is directly related with pathogenesis of the disease, and others have strong linkage disequilibrium with HLA-B51. Some other genes such as IL1, Factor V and ICAM-1, KIR and eNOS assumed to take a part in the pathogenesis are settled out of the MHC region. In patients with BD, several abnormalities in innate and acquired immunity were detected. Mainly, the hypersensitivity of T lymphocytes to different types of antigens plays a critical role in the pathogenesis. However, it is not clear that whether defective signal transduction or antigen presenting cell (APC) dysfunction is responsible for T cell hypersensitivity. Cytokines and chemokines secreted from APCs and T cells are suggested to cause the neutrophil hyperactivation. Activated neutrophils secrete some cytokines, which prime themselves and also stimulate Th1 cells. These relationships among APCs, Th1 lymphocytes and neutrophils constitute the basis of immune responses in BD. In this review, we focus on the possible role of APC in the pathogenesis of BD with an attempt to take attention of researchers in this field to these cells at the crossroads of innate and adaptive immunity, and discuss other potential contributors including cells of the immune system and mediators.

Antigen-Presenting Cells↗