Материал из hpluswiki
Перейти к навигации Перейти к поиску

Clathrin light chain A (Lca)


Reduced CTLA-4 protein and messenger RNA expression in umbilical cord blood T lymphocytes.

A favorable incidence and severity of graft-vs-host disease is observed in patients transplanted with banked, unrelated, HLA-mismatched umbilical cord blood (UCB) grafts, while the incidence of malignant relapse remains low. CTLA-4 mediates negative T-cell signaling and may contribute to the development of allogeneic tolerance. In this study, we compared protein and mRNA expression of CTLA-4 in stimulated UCB and adult peripheral blood T cells. T cells were isolated from UCB and adult peripheral blood and stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. Cells were immunostained and analyzed by flow cytometry for both surface and intracellular expression of CTLA-4 in the presence and absence of cyclosporin A, and kinetics of CTLA-4 expression compared. CTLA-4 mRNA expression was measured using quantitative real-time polymerase chain reaction. NFAT1 protein levels were measured by Western blot analysis. These studies demonstrate reduced surface and intracellular expression of CTLA-4 in stimulated UCB T cells compared to adult controls. Furthermore, reduced CTLA-4 protein expression in UCB T cells was noted to be in part transcriptionally regulated, as CTLA-4 mRNA levels also were significantly lower. Reduced CLTA-4 expression by UCB T cells followed the kinetics of delayed and reduced expression of the transcription factor NFAT1 by UCB T lymphocytes during primary stimulation. Moreover, cyclosporin A, which is known to modulate NFAT activation, reduced CTLA-4 protein expression in adult and UCB T cells. Reduced expression of the key regulatory proteins CTLA-4 and NFAT-1 may contribute to favorable UCB T lymphocyte allogeneic responses.

MeSH Terms

  • Abatacept
  • Adult
  • Aging
  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • Cell Division
  • Cyclosporine
  • DNA-Binding Proteins
  • Fetal Blood
  • Flow Cytometry
  • Gene Expression Regulation
  • Graft vs Host Disease
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immune Tolerance
  • Immunoconjugates
  • Immunosuppressive Agents
  • Infant, Newborn
  • Lymphocyte Activation
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Polymerase Chain Reaction
  • RNA, Messenger
  • T-Lymphocytes
  • Transcription Factors
  • Transcription, Genetic