Immune regulation by peripheral suppressor T cells induced upon homotypic T cell/T cell interactions.
We have shown previously that homotypic interaction of resting memory CD4 T cells with activated T cells induces the production of cytokines with immunoregulatory potential (IL-10, IL-4) from the former. Here, we analyzed the effector functions of these T cells stimulated by homotypic T cell interaction. T cells induced upon homotypic T cell interaction expressed CD25 and reduced levels of CD127 and produced TGF-β. Functionally, homotypic T cell interaction-induced T cells were anergic and inhibited the proliferation of CD25-negative T cells as potently as naturally occurring CD25-positive Tregs in vitro. They also prevented clonotypic expansion of OVA TCR tg T cells in BALB/c mice upon antigenic challenge in vivo. The generation of suppressor T cells by homotypic T cell contact is anchored and tuned through interactions of LFA-1 and its ligands ICAM-1, ICAM-2, and ICAM-3. Together, the data suggest a negative-feedback mechanism of specific immunity involving bystander-activated memory T cells.
Thümmler
Katja
K
University of Munich, Pettenkoferstrasse 8a, Munich, Germany. alla.skapenko@med.uni-muenchen.de
Leipe
Jan
J
Ramming
Andreas
A
Schulze-Koops
Hendrik
H
Skapenko
Alla
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013491:Suppressor Factors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell; D013491:Suppressor Factors, Immunologic