The role of TCR stimulation and TGF‐β in controlling the expression of CD94/NKG2A receptors on CD8 T cells

• Published in: European journal of immunology 2005-03, Vol.35 (3), p.766-775
• Main Authors: Gunturi, Anasuya, Berg, Rance E., Crossley, Emily, Murray, Sean, Forman, James
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - immunology; Antigens, CD - metabolism; CD8 T cells; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD94; Cytokines; Flow Cytometry; Gene Expression; Lectins, C-Type - immunology; Lectins, C-Type - metabolism; Listeria monocytogenes - immunology; Listeriosis - immunology; Mice; NK Cell Lectin-Like Receptor Subfamily C; NK Cell Lectin-Like Receptor Subfamily D; Receptors, Antigen, T-Cell - immunology; Receptors, Antigen, T-Cell - metabolism; Receptors, Immunologic - immunology; Receptors, Immunologic - metabolism; Receptors, Natural Killer Cell; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; T cell receptors; Transforming Growth Factor beta - immunology; Transforming Growth Factor beta - metabolism; Up-Regulation
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200425735

Following antigen recognition, murine CD8 T cells express CD94/NKG2A receptors. Our results show that this up‐regulation occurs rapidly in vitro and is accompanied by an ∼8‐fold increase in CD94 and ∼125‐fold increase in NKG2A mRNA. In contrast, only a twofold increase in NKG2C mRNA is noted. The addition of TGF‐β, but not IL‐10, IL‐12 or IL‐15, leads to a further increase in cell membrane expression of these receptors, as well as a ∼6‐fold increase in mRNA for both chains. TGF‐β also increases CD94/NKG2A expression on memory CD8 T cells that are re‐exposed to antigen. The effect of TGF‐β on increasing CD94/NKG2A expression on both naive and memory CD8 T cells occurs only when there is a concurrent stimulation through the TCR. In contrast, TGF‐β does not increase expression of CD94/NKG2A on resting or activated NK cells. We also show by using purified CD8 T cells, that TGF‐β acts directly on these cells. These results implicate a role for both antigen and TGF‐β in increasing expression of inhibitory CD94/NKG2A receptors on CD8 T cells.