Tissue infiltrating lymphocytes: the role of cytokines in their growth and differentiation.

The second half of the XX century saw a continuous improvement in the understanding of cellular immunology. The discovery of monoclonal antibodies permitted to identify several functional T-cell subpopulations, characterized by a specific pattern of cytokine secretion. According to their functions, cytokines have been divided into two main groups: pro- and anti- inflammatory. Cytokines are involved in several aspects of immunity and inflammation. Because of its importance in host defence, the cytokine system is redundant and therefore different cytokines may perform similar activities. Although cytokines and inflammatory processes have been studied widely in the peripheral blood, it is our opinion that the most important pathogenetic events occur at the tissue level, therefore the study of Tissue-infiltrating lymphocytes (TIL) is of foremost importance. In this review we therefore focus on the cytokine microenvironment; different local tissue cytokine-cocktails can modulate and regulate T-cell proliferation and differentiation. CD4+ T-cells are not characterized by irreversibly differentiated endpoints, but there is an evident plasticity of these cells with a large possibility of differentiation options. We will discuss the issue and give examples of the diseases where the study of TIL and their microenvironment are most significant, including tumors, primary immunodeficiencies, rheumathoid arthritis, inflammatory skin diseases and coronary disease. We also review the role of apoptosis and the environment of mucosal immunity.