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.