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