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(American Journal of Pathology. 2004;164:409-417.)
© 2004 American Society for Investigative Pathology

Plasma Cell-Like Morphology of Th1-Cytokine-Producing Cells Associated with the Loss of CD3 Expression

Guillaume Page^*, Arne Sattler, Sabine Kersten, Andreas Thiel, Andreas Radbruch and Pierre Miossec^*

From INSERM U403 and the Departments of Immunology and Rheumatology,^* Hôpital Edouard Herriot, Lyon, France; and the Deutsches Rheumaforschungszentrum Berlin, Berlin, Germany

Here we clarified the morphology and phenotype of interleukin (IL)-17- and interferon (IFN)--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--producing cells was evaluated by immunohistochemistry using the CD3 and CD4 T-cell markers, the CD20, CD38, and 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-+ 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--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.

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