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Regulation of surface and intracellular expression of CTLA-4 on human peripheral T cells
X B Wang1, C Y Zheng, R Giscombe
1Immunological Research Unit, Center for Molecular Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Abstract:
Cytotoxic T-lymphocyte-associated antigen (CTLA-4) is an important downregulator of T-cell activation. In order to analyze the expression and regulation of CTLA-4 on human peripheral T cells, CTLA-4 mRNA and protein expression were determined using analysis by reverse transcription-polymerase chain reaction (RT-PCR) and FACs, respectively. Intracellular CTLA-4 was constitutively expressed in unstimulated CD4+ and CD8+ T cells. Interleukin (IL)-2 induced a dose-dependent increase of both intracellular and surface expression of CTLA-4 (CD152). Most of the CD4+ and CD8+ cells expressing CTLA-4 also expressed CD25. Interferon (IFN)-gamma induced the upregulation of CTLA-4 expression via antigen-presenting cells (APC) activation. The CTLA-4delTM mRNA (550 bp) had a shorter half-life than the full length CTLA-4 mRNA and the expression was downregulated upon activation of the cells by treatment with IL-2. Given an inhibitory role of CTLA-4 and CD4+ CD25+ T cells in immune responses, the present findings suggest that IL-2-induced immunosuppression may result from its stimulatory effect of the CTLA-4 expression.
Insights
Cytotoxic T-lymphocyte-associated antigen (CTLA-4) is constitutively expressed on human T cells. Interleukin-2 (IL-2) increases CTLA-4 expression, suggesting a role in IL-2-induced immunosuppression.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Cytotoxic T-lymphocyte-associated antigen (CTLA-4) is a key regulator of T-cell activation.
- Understanding CTLA-4 expression and regulation is crucial for immune response modulation.
Purpose of the Study:
- To investigate the expression and regulation of CTLA-4 in human peripheral T cells.
- To elucidate the role of Interleukin-2 (IL-2) and Interferon-gamma (IFN-γ) in CTLA-4 modulation.
Main Methods:
- CTLA-4 mRNA and protein levels were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FACs).
- Expression was assessed in unstimulated and stimulated CD4+ and CD8+ T cells.
Main Results:
- Intracellular CTLA-4 was constitutively expressed in unstimulated T cells (CD4+ and CD8+).
- IL-2 dose-dependently increased both intracellular and surface CTLA-4 (CD152) expression.
- IFN-γ upregulated CTLA-4 expression through antigen-presenting cells (APCs).
- A shorter CTLA-4delTM mRNA variant showed reduced stability and was downregulated by IL-2.
Conclusions:
- IL-2 stimulation enhances CTLA-4 expression on T cells, potentially contributing to immunosuppression.
- The findings highlight the intricate regulation of CTLA-4 and its implications in immune responses.