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Skin-induced tolerance and its reversal by Toll-like receptor ligands

100%

Szczepanik M.

Archivum Immunologiae et Therapiae Experimentalis

2007

tom 55

nr 3

161-172

In 1970, Gershon was the first to propose that T cells, in addition to their helper activity, can also play a role as regulatory cells capable of suppressing immune responses. However, the initial strong interest in T cell-mediated suppression was followed by a period of doubt and skepticism. Since the late 1990s the 'S' word started to be used in immunology again and interest in T suppressor cells has grown, ushering in a new renaissance for the field. In this article the author presents the current knowledge about a new subject called 'skin-induced tolerance'. Suppression is induced via epicutaneous immunization and is described in both Th1- and Tc1-mediated contact sensitivity reactions. The subject of skin-induced tolerance is also considered in the regulation of experimental models of autoimmune diseases such as allergic autoimmune encephalomyelitis and collagen-induced arthritis and finally in an animal model of graft rejection. The last part of this presentation will introduce the very fresh subject of ?contrasuppression', or the reversal of skin-induced suppression.

TCR alpha beta+ CD8+ and TCR gamma delta lymphocytes inhibit the capability of peritoneal macrophages to induce contact hypersensitivity

38%

Majewska M. , Zajac K. , Zemelka M. , Sura P. , Gryglewski A. , Szczepanik M.

Folia Biologica

2009

tom 57

nr 1-2

23-27

Macrophages (Mf) play an important role in induction and regulation of the immune response. It was shown previously that subcutaneous injection of hapten conjugated macrophages (TNP-Mf) induces the contact hypersensitivity (CHS) response, whereas intravenous (i.v.) or intraperitioneal administration of TNP-Mf results in unresponsiveness as a result of induced T suppressor (Ts) cells. The aim of this study was to determine if different T cell populations influence macrophages to become inducers of immunological suppression. Our findings show that indeed i.v. injection of TNP labeled macrophages isolated from control mice into syngenic recipients induces unresponsiveness. However, i.v. administration of TNP substituted macrophages isolated from TCR'-/-, TCR*-/- and $2m-/- mice induces strong CHS similar to that observed after skin painting with TNP-Cl.Moreover, it was shown that TNP conjugated macrophages isolated from CD1d-/- mice were still able to promote immunosuppression when injected intravenously. This suggests that TCR'$+ CD8+ and TCR(*+ lymphocytes stimulate macrophages to induce immunosuppression instead of a strong CHS reaction, whereas CD1d dependent NKT cells are not involved in negative regulation of macrophage function.