Activation of HLA-DR and interleukin-6 gene transcription in resting T cells via the CD2 molecule: relevance to chronic immune-mediated inflammation.
Only a minority of T cells at cell-mediated immune lesions are antigen specific. In the lesions of human autoimmune disease, such as the synovial membrane in rheumatoid arthritis, the T cells are activated as shown by a variety of phenotypic and functional changes including the expression of HLA-DR and the production of interleukin-6 (IL-6). The stimulatory pathway involved is unknown but does not seem to involve the T-cell receptor. Alternative pathways of activation which may be involved include the CD2 molecule. It is shown that the formation of sheep red blood cell (SRBC) rosettes with resting T cells from human peripheral blood, which is equivalent to CD2/LFA-3 binding, leads to the de novo transcription of the HLA-DR and IL-6 genes and the expression of HLA-DR on the surface of the T cells. There was no transcription of the interleukin-2 (IL-2) or the interleukin-2 receptor (IL-2R) genes and Tac expression was not seen. The rosetted T cells did not proliferate. These are all characteristics of T cells at chronic inflammatory sites. It is concluded that receptor-ligand interactions between CD2/LFA-3, which are expressed in increased amounts in the rheumatoid joint, may be one pathway by which antigen non-specific T cells are recruited as effector cells in lesions of human autoimmune disease.
Rheumatology Unit, United Medical School, Guy's Hospital, London, UK.
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Linardopoulos
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Corrigall
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Panayi
D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018801:CD2 Antigens; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007930:Leucine / Q000031:analogs & derivatives; D008213:Lymphocyte Activation / Q000276:immunology; D010835:Phytohemagglutinins; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D006684:HLA-DR Antigens; D015850:Interleukin-6; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; C030365:leucine methyl ester; D007930:Leucine; D013755:Tetradecanoylphorbol Acetate