Regulation of surface and intracellular expression of CTLA-4 on human peripheral T cells.
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.
Wang
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XB
Immunological Research Unit, Center for Molecular Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Zheng
C Y
CY
Giscombe
R
R
Lefvert
A K
AK
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D060908:CTLA-4 Antigen; D002462:Cell Membrane / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018796:Immunoconjugates; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007424:Intracellular Fluid / Q000276:immunology; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012995:Solubility; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D017931:DNA Primers; D018796:Immunoconjugates; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D003208:Concanavalin A; D000069594:Abatacept; D007371:Interferon-gamma