The T-Cells’ Role in Antileukemic Reactions - Perspectives for Future Therapies’

1.1 Background (Schmid, Schmetzer) Highly specialized and sensitive defence against infections as well as tumors is provided in great part by the adaptive, T-cell-mediated part of our immune system. Those T-cell specialists arise out of a cell pool of 25-100 million distinct naive T-cell clones, after a very efficient priming phase by dendritic cells (DC), that present antigens in the context of major histocompatibility complexes (MHC), T-cell receptors (TCR) and costimulatory signals. It is well known, that T-cells are most important effectors of cellular tumor immunity and carry long lasting memory. Therefore recent tumor research has focused on the development and improvement of T-cell based immunotherapies (Barrett & Le Blanc, 2010; Smits et al., 2011). The T-lymphocyte pool includes naive (Tnaive), effector (Teff), effector memory (Tem) and central memory (Tcm), either CD8 or CD4 T-cells. After an antigen driven TCR engagement Tnaive proliferate and give rise to large numbers of Teff. Most of them die after depleting target cells. Some ‘memory T-cells’ of either Tcm or Tem phenotype remain, persist and can differentiate to Teff after a re-challenge with antigens. It has been demonstrated that memory T-cells are able to self-renewal and differentiation (Sallusto et al., 2005). However antitumor immunity is limited by regulatory T-cells (Treg) that are in general responsible for the prevention of autoimmunity, regulation of inflammatory antimicrobial or antitumor reactions and are regarded as the mediators of tolerance (Vignali et al., 2008). Treg reactions can be either mediated by inhibitory cytokines (IL-10, IL-35, TGF-s), Granzyme A/B dependent cytolysis, CD25 dependent IL-2 deprivation-mediated apoptosis, adenosine receptor mediated immunosuppression of DCs’ maturation (Vignali et al., 2008). Treg subtypes can be identified by their expression profiles and be subdivided in resting or activated Tregs of either CD4 or CD8 subtype (Miyora et al., 2009; Jordanova et al., 2008; Schick et al., 2011). Resting Tregs can convert to activated Tregs after proliferation. The functional repertoire of T-cells depends on their survival and their cooperation via cellular contact and the secretion of humoral factors. Improved knowledge of these properties should contribute to detect or select T-cells with defined markers or functional profiles for adoptive therapy.