Epicutaneous immunization induces alphabeta T-cell receptor CD4 CD8 double-positive non-specific suppressor T cells that inhibit contact sensitivity via transforming growth factor-beta. Immunology 2005 May;115(1):42-54
Date
04/12/2005Pubmed ID
15819696Pubmed Central ID
PMC1782121DOI
10.1111/j.1365-2567.2005.02127.xScopus ID
2-s2.0-17844410676 (requires institutional sign-in at Scopus site) 56 CitationsAbstract
Since it was previously shown that protein antigens applied epicutaneously in mice induce allergic dermatitis mediated by production of T helper 2 (Th2) cytokines we postulated that this might induce suppression of Th1 immunity. Here we show that epicutaneous immunization of normal mice with a different protein antigen applied on the skin in the form of a patch induces a state of subsequent antigen-non-specific unresponsiveness caused by suppressor T cells (Ts) that inhibit sensitization and elicitation of effector T-cell responses. Suppression is transferable in vivo by alphabeta-T-cell receptor CD4(+) CD8(+) double positive lymphocytes harvested from lymphoid organs of skin patched animals and are not major histocompatibility complex-restricted nor antigen specific. Both CD25(+) and CD25(-) CD4(+) CD8(+) T cells are able to suppress adoptive transfer of Th1 effector cells mediating cutaneous contact sensitivity. In vivo treatment with monoclonal antibodies showed that the cytokines interleukin (IL)-4, IL-10 and transforming growth factor-beta (TGF-beta) are involved in the induction of the Ts cells. Additionally, using IL-10(-/-) mice we found that IL-10 is involved in skin induced tolerance. Further in vitro experiments showed that lymph node cells of skin tolerized mice non-specifically suppress [(3)H]thymidine incorporation by antigen-stimulated immune cells and this effect can be abolished by adding anti-TGF-beta, but not anti-IL-4 nor anti-IL-10 antibodies. These studies indicate the crucial role of TGF-beta in skin induced tolerance due to non-antigen-specific Ts cells and also show that IL-4, IL-10 and TGF-beta play an important role in the induction of epicutaneously induced Ts cell suppression.
Author List
Szczepanik M, Bryniarski K, Tutaj M, Ptak M, Skrzeczynska J, Askenase PW, Ptak WAuthor
Monika Tutaj Research Scientist II in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Administration, CutaneousAdoptive Transfer
Animals
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cytokines
Dermatitis, Contact
Dose-Response Relationship, Immunologic
Immune Tolerance
Immunization
Lymph Nodes
Male
Mice
Mice, Inbred BALB C
Mice, Inbred CBA
Receptors, Antigen, T-Cell, alpha-beta
Skin
T-Lymphocytes, Regulatory
Transforming Growth Factor beta