Abstracts (complete list) - Wissenschaft Online

Katja Thümmler, Andreas Ramming, Alla Skapenko, Hendrik Schulze-Koops
Regulation of specific immunity by homotypic T cell/T cell
interaction
Specialized T cells with a regulatory phenotype are most important in controlling specific
immunity to self-antigens and, thus, in maintaining peripheral tolerance. Different T cell
subsets with a regulatory phenotype have been described that may develop in the
periphery in response to T cell stimulation. Differentiation of T cells, in turn, is regulated
by cytokines and a variety of cell surface receptors, for which activated effector T cells
express the appropriate ligands. Here, we tested the hypothesis, that homotypic T cell
interactions may permit the induction of T cells with a regulatory phenotype. CD4 T cells
were isolated from the peripheral blood of healthy donors and activated under Th1 or
Th2 conditions. The resulting effector cells were fixed with paraformaldehyd and
cocultured together with syngeneic freshly isolated resting CD4 memory or naive T cells
but in the absence of specific T cell stimulatory factors such as mAbs to T cell surface
molecules, antigens or mitogens. After five days of coculture, the phenotype and
function of the resulting cells were analyzed by assessing their production of cytokines
by ELISA, flow cytometric analysis of cytoplasmic cytokines and realtime PCR and by
determining their ability to prevent the proliferation of autologous responder T cells. T
cells that had been generated in the presence of fixed Th2 effector cells produced IL-4,
but little IFN-γ. In contrast, Th1 effector cells promoted the development of IL-10 and
IFN-γ double-producing T cells. Of interest, both T cell populations that were generated
by homotypic T-T cell interactions strongly inhibited the proliferation of CD25 negative
responder T cells in a dose dependent manner. Although T-T cell-generated effector
cells did not express Foxp3 their regulatory capacity was comparable to that of
conventional CD25 positive Tregs. The results indicate that homotypic T-T cell
interaction induces the generation of Th1-like or Th2-like effector T cells with a
regulatory phenotyp, providing a novel potential negative feedback mechanism to
control sustained T cell driven immunity.