TY - JOUR
T1 - Functional subsets of CD4 T cells in rheumatoid synovitis
AU - Namekawa, Takashi
AU - Wagner, Ulf G.
AU - Goronzy, Jörg J.
AU - Weyand, Cornelia M.
PY - 1998
Y1 - 1998
N2 - Objective. To identify the functional properties of CD4+ CD28- T cells, which accumulate and clonally expand in patients with rheumatoid arthritis (RA). Methods. The gene expression of molecules involved in T cell effector functions was compared in CD4+ CD28- and CD4+ CD28+ T cell clones. The expression of differentially up-regulated genes was confirmed by flow cytometry of T cells and by 2-color immunohistochemistry of rheumatoid synovial tissue. Cytotoxicity of CD4+ CD28- T cells was tested by anti-CD3 redirected lysis of Fc receptor-positive target cells. Results. CD4+ CD28- T cell clones lacked messenger RNA for the CD40 ligand (CD40L) but transcribed the perforin gene. Perforin was also found in freshly isolated CD4+ CD28- peripheral blood lymphocytes from RA patients. CD4+ CD28-, but not CD4+ CD28+, T cell clones lysed Fc receptor-bearing target cells. CD4+ perforin- positive T cells were present in the synovial tissue, where their frequency correlated with the expansion of the CD4+ CD28- compartment in the periphery. Among tissue-infiltrating CD4+ T cells, only the CD40L-negative subset expressed perforin transcripts. Conclusion. Clonally expanded CD4+ CD28- T cells are functionally specialized for killing, while they lack the ability to provide B cell help. Tissue-infiltrating CD4+ T cells can be subdivided phenotypically and functionally into at least 2 distinct subsets based on their expression of perforin and CD40L. Because the expansion of CD4+ CD28- T cells is associated with extraarticular RA, T cell-mediated cytotoxicity may be particularly important in these most severe complications of RA.
AB - Objective. To identify the functional properties of CD4+ CD28- T cells, which accumulate and clonally expand in patients with rheumatoid arthritis (RA). Methods. The gene expression of molecules involved in T cell effector functions was compared in CD4+ CD28- and CD4+ CD28+ T cell clones. The expression of differentially up-regulated genes was confirmed by flow cytometry of T cells and by 2-color immunohistochemistry of rheumatoid synovial tissue. Cytotoxicity of CD4+ CD28- T cells was tested by anti-CD3 redirected lysis of Fc receptor-positive target cells. Results. CD4+ CD28- T cell clones lacked messenger RNA for the CD40 ligand (CD40L) but transcribed the perforin gene. Perforin was also found in freshly isolated CD4+ CD28- peripheral blood lymphocytes from RA patients. CD4+ CD28-, but not CD4+ CD28+, T cell clones lysed Fc receptor-bearing target cells. CD4+ perforin- positive T cells were present in the synovial tissue, where their frequency correlated with the expansion of the CD4+ CD28- compartment in the periphery. Among tissue-infiltrating CD4+ T cells, only the CD40L-negative subset expressed perforin transcripts. Conclusion. Clonally expanded CD4+ CD28- T cells are functionally specialized for killing, while they lack the ability to provide B cell help. Tissue-infiltrating CD4+ T cells can be subdivided phenotypically and functionally into at least 2 distinct subsets based on their expression of perforin and CD40L. Because the expansion of CD4+ CD28- T cells is associated with extraarticular RA, T cell-mediated cytotoxicity may be particularly important in these most severe complications of RA.
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U2 - 10.1002/1529-0131(199812)41:12<2108::AID-ART5>3.0.CO;2-Q
DO - 10.1002/1529-0131(199812)41:12<2108::AID-ART5>3.0.CO;2-Q
M3 - Article
C2 - 9870867
AN - SCOPUS:0032417125
SN - 0004-3591
VL - 41
SP - 2108
EP - 2116
JO - Arthritis and rheumatism
JF - Arthritis and rheumatism
IS - 12
ER -