CLTA

Clathrin light chain A (Lca)

Publications

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

PubMed

Full text

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