Homotypic T-cell/T-cell interaction induces T-cell activation, proliferation, and differentiation.
Activated CD4 T cells might induce T-cell activation from CD4 resting T cells in the absence of antigen presenting cells through interaction of activation-induced surface molecules (e.g., CD80, CD86, CD70, major histocompatibility complex class II) and their ligands constitutively expressed on resting T cells. Supporting this hypothesis, CD4 memory T cells proliferated in response to contact with activated T cells and expressed activation markers, such as CD25, CD30, and CD69. Analysis of their cytokine profile revealed differentiation of interleukin (IL)-10 and interferon-gamma double-producing cells in response to contact with activated T helper (Th) 1 effector cells, and interleukin (IL)-4-producing cells in response to contact with activated Th2 effector cells. Whereas neutralization of interferon-gamma or IL-4 during co-culture did not diminish the frequency of the arising cytokine-producing cells, separation of the responder cells from effector cells significantly decreased cytokine secretion. Specific blocking of particular receptor/ligand interactions denoted above could not prevent cytokine production induced by T-cell/T-cell interaction. However, blockade of all of the receptor/counterreceptor pairs significantly inhibited cytokine production, although not completely. Given the immunomodulatory capacity of IL-4 and IL-10, these findings might indicate a novel contact dependent negative feedback mechanism to control T-cell-driven immunity.
Ramming
Andreas
A
Division of Rheumatology, Medizinische Poliklinik, University of Munich, Munich, Germany.
Thümmler
Katja
K
Schulze-Koops
Hendrik
H
Skapenko
Alla
A
D000938:Antigen-Presenting Cells / Q000276:immunology; D002450:Cell Communication; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D007113:Immunity, Innate; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma