T-Lymphocyte Recognition of Antigen in Association with Gene Products of the Major Histocompatibility Complex

Schwartz, Ronald H.

doi:10.1146/annurev.iy.03.040185.001321

Cited by 875 publications

(238 citation statements)

References 25 publications

Supporting

Mentioning

231

Contrasting

Order By: Relevance

“…Class 1 MHC molecules are involved in antigen presentation by antigen-presenting cells to cytotoxic T lymphocytes (CTL) (33), and the possibility of increased T cell-mediated synovial cell lysis in the inflammatory microenvironment of RA joints is purely speculative at this time. Precedence for this concept comes from studies in which I F N y stimulated virus-infected fibroblasts, which expressed more class I MHC antigen, were more susceptible to CTL-mediated lysis than were comparable non-IFN y induced fibroblasts (34).…”

Section: Discussionmentioning

confidence: 99%

Role of cytokines in inflammatory synovitis

Chin

Winterrowd

Krzesicki

et al. 1990

Arthritis & Rheumatism

118

View full text Add to dashboard Cite

This study was undertaken in an effort to understand the role of cytokines in T lymphocyte trafficking into inflamed synovium and in the potential enhancement of antigen presentation by human synovial fibroblasts. We found that interleukin-lp (IL-lp), tumor necrosis factor a (TNFa), and interferon-y (IFNy) each increased the cell surface expression of intercellular adhesion molecule I (ICAM-I) on human synovial fibroblasts in a dose-and time-dependent manner. Maximal ICAM-1 expression occurred within 8 hours of induction, with the following order of efficacy: IFNy > TNFa > IL-1p. The number of cells bearing the ICAM-1 antigen also increased, from a basal level of -30% to more than 83% after cytokine induction (for all 3 cytokines). ICAM-1 expression rapidly decreased fdlowing cytokine removal. The expression of lymphocyte function-associated antigen 3 was also examined, but it was not changed by any of the 3 cytokines. Class I major histocompatibility complex antigen expression was increased modestly by all 3 cytokines, and expression was maximal by 24 hours after treatment. Only IFNy induced HLA class I1 antigen expression, and this expression persisted for up to 6 days following removal of the lymphokine. IL-6 and granulocyte-macrophage colony- stimulating factor had no effect on any of the parameters examined. Our data support an interactive role for inflammatory cytokines and the expression of adhesion ligands and HLA antigens by human synovial fibroblasts in the pathogenesis of synovial inflammation in rheumatoid arthritis.Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized in part by the proliferation of pannus tissue in diseased joints, which leads to eventual degradation of the articular cartilage and the subchondral bone (1)(2)(3). It has been demonstrated that the RA synovium contains cells that express HLA-DR antigens (4-7). There is also evidence that indicates that cells populating the inflamed tissue lining the RA joint have adhesion molecules as ligands for homing receptors on circulating T lymphocytes (8,9). It is hypothesized that the increased adhesiveness of the inflamed synovial tissue may play a central role in lymphocyte homing and retention in the diseased joint. The current study was initiated in an effort to elucidate cellular mechanisms that may be involved in chronic inflammatory synovitis. We examined the time and dose effects of various cytokines present in the inflammatory microenvironment in RA (10) on the expression of adhesion ligands intercellular adhesion molecule I (ICAM-1) and lymphocyte function-associated antigen 3 (LFA-3), and the expression of class I and class I1 major histocompatibility complex (MHC) antigens, 4 fibroblast cell surface molecules whose regulation may play critical roles in synovial inflammation.In previous studies, interferon-y (IFNy) has been shown to induce the expression of class I1 MHC antigens on synovial fibroblasts (1 l), and ICAM-1 has MATERIALS AND METHODSRecombinant cytokines and antibodies. Recombinant human i...

show abstract

Section: Discussionmentioning

confidence: 99%

Role of cytokines in inflammatory synovitis

Chin

Winterrowd

Krzesicki

et al. 1990

Arthritis & Rheumatism

118

View full text Add to dashboard Cite

show abstract

“…DP thymocytes are selected on the basis of their ability to recognize selfpeptide/major histocompatibility complex (MHC) antigen by their T-cell receptors (TCRs). 1,2 Selected thymocytes further differentiate to become mature SP thymocytes and are self-MHC restricted in antigen recognition and tolerant to selfantigens. 3,4 Signaling through TCR, costimulatory molecules, and Notch1 is known to be important for selections and further differentiation of DP thymocytes into SP cells.…”

Section: Introductionmentioning

confidence: 99%

Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter

Jang

Choi

et al. 2005

Cell Death Differ

View full text Add to dashboard Cite

One notable phenotypic change during the differentiation of immature thymocytes into either mature CD4 or CD8 singlepositive lineages is the acquisition of a resistance to glucocorticoid (GC)-induced apoptosis. We have previously reported that SRG3 is critical in determining the sensitivity for the GC-induced apoptosis in developing thymocytes. We report here that Notch signaling downregulates the transcriptional activation of SRG3 through N-box and/or E-box elements on its promoter. RBP-J represses SRG3 transcription through the N-box motif. On the other hand, Deltex1 competitively inhibits the binding of p300 to E2A/HEB protein bound to the E-box elements and represses the SRG3 promoter activity. Moreover, enforced expression of Deltex1 restored double-positive (DP) thymocyte survival from the GC-induced apoptosis. Our results suggest that Notch signaling confers differentiating DP thymocytes resistance to GCs by regulating the SRG3 expression through Deltex1, and that Deltex1 and SRG3 may play a significant role during DP thymocyte maturation.

show abstract

“…The macrophage plays an important role not only in the antigen processing and antigen presentation but also in the induction of T-cell-mediated immunity [2]. The disease is characterized by the defective cell-mediated immunity [3], and polyclonal B-cell activation [4] whose induction is secondary to a primary Mf defect [5].…”

Section: Introductionmentioning

confidence: 99%

Macrophage Heterogeneity, Antigen Presentation, and Membrane Fluidity: Implications in Visceral Leishmaniasis

et al. 2001

View full text Add to dashboard Cite

Morphological and functional heterogeneity of the splenic macrophage (Mf) population was studied in Leishmania donovani (LD) infected BALB/c mice. On a discontinuous percoll gradient two distinct Mf populations were separated. They differed significantly in size as evident from Scanning Electron Microscopy (SEM). Morphologically, the bigger Mf (LM) showed surface projections, whereas the smaller Mf (SM) was round. As regards the antigen-presenting abilities, the LM of infected animals showed defective antigen-presenting abilities at a later stage of the disease, i.e. 6 months post infection ( 6 I-LM) but not earlier, whereas the SM population remained functionally intact throughout the course of the infection. Further, the 6 I-LM showed a much enhanced A d status as compared to their controls. Interestingly, both the 6 I-LM and the control set showed a comparable level of binding of a known A d restricted peptide. Despite the presence of sufficient A d molecules and the ability to bind the appropriate peptide, 6 I-LM were unable to stimulate peptide specific T-cell hybridoma. Further, the 6 I-LM showed an increase in membrane fluidity and distorted morphology with membrane fissure and blebs as evident from SEM. It is possible that an increase in the membrane fluidity may lead to the defective antigen-presenting ability of 6 I-LM. Thus, the LD infection functionally keep the 6 I-LM out of antigen presentation and this may contribute to the defective cell mediated immune response in leishmaniasis.

show abstract

T-Lymphocyte Recognition of Antigen in Association with Gene Products of the Major Histocompatibility Complex

Cited by 875 publications

References 25 publications

Role of cytokines in inflammatory synovitis

Role of cytokines in inflammatory synovitis

Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter

Macrophage Heterogeneity, Antigen Presentation, and Membrane Fluidity: Implications in Visceral Leishmaniasis

Contact Info

Product

Resources

About