Plasma cell-like morphology of Th1-cytokine-producing cells associated with the loss of CD3 expression.
Here we clarified the morphology and phenotype of interleukin (IL)-17- and interferon (IFN)-gamma-producing cells in both in vitro and in vivo situations. Oligoclonal activation of normal peripheral blood mononuclear cells with the superantigen Staphylococcus aureus enterotoxin B and polyclonal activation with phorbol myristate acetate/phytohemagglutinin were used as in vitro models. This study was extended to various in vivo situations such as rheumatoid arthritis, dermatomyositis, and normal activated lymph nodes. The phenotype of IL-17- and IFN-gamma-producing cells was evaluated by immunohistochemistry using the CD3 and CD4 T-cell markers, the CD20, CD38, kappa and lambda light chain B-cell lineage markers. The expression of two chemokine receptors, CCR6 and CCR7, involved with their associated ligands CCL20 and CCL19/CCL21 in the migration of T lymphocytes, was evaluated in tissue sections. After both polyclonal and oligoclonal activation, IL-17+ and IFN-gamma+ cells acquired a plasma cell-like morphology associated with a high secretory activity, the reduced expression of CD3, and no change of CD4 expression. In rheumatoid arthritis, dermatomyositis, and activated lymph nodes, both IL-17- and IFN-gamma-producing cells had the same morphology. These Th1 cytokine-producing cells were CD4(+)-, CD3-, and B-cell lineage marker-negative. In both in vitro and in vivo situations, expression of CCR6 or CCR7 was not associated with a particular subset. In conclusion, activated T-helper CD4(+) T cells, by their release of cytokines, seem to have functional similarities with plasma cells secreting immunoglobulins.
Page
Guillaume
G
INSERM U403 and the Department of Immunology, Hôpital Edouard Herriot, Lyon, France.
Sattler
Arne
A
Kersten
Sabine
S
Thiel
Andreas
A
Radbruch
Andreas
A
Miossec
Pierre
P
D015703:Antigens, CD / Q000096:biosynthesis; D001172:Arthritis, Rheumatoid / Q000276:immunology; D017252:CD3 Complex / Q000096:biosynthesis*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003882:Dermatomyositis / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D010641:Phenotype; D010950:Plasma Cells / Q000166:cytology; D019707:Receptors, Chemokine / Q000096:biosynthesis; D018417:Th1 Cells / Q000166:cytology* / Q000378:metabolism*
D015703:Antigens, CD; D017252:CD3 Complex; D016207:Cytokines; D020381:Interleukin-17; D019707:Receptors, Chemokine; D007371:Interferon-gamma