PMID- 11895781 OWN - NLM STAT- MEDLINE DCOM- 20020502 LR - 20211203 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 99 IP - 7 DP - 2002 Apr 1 TI - CD4(+) and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. PG - 2468-76 AB - Interleukin-10 (IL-10)-treated dendritic cells (DCs) induce an alloantigen- or peptide-specific anergy in various CD4(+) and CD8(+) T-cell populations. In the present study, we analyzed whether these anergic T cells are able to regulate antigen-specific immunity. Coculture experiments revealed that alloantigen-specific anergic CD4(+) and CD8(+) T cells suppressed proliferation of syngeneic T cells in a dose-dependent manner. The same effect was observed when the hemagglutinin-specific CD4(+) T-cell clone HA1.7 or tyrosinase-specific CD8(+) T cells were cocultured with anergic T cells of the same specificity. Anergic T cells did not induce an antigen-independent bystander inhibition. Suppression was dependent on cell-to-cell contact between anergic and responder T cells, required activation by antigen-loaded DCs, and was not mediated by supernatants of anergic T cells. Furthermore, anergic T cells displayed an increased extracellular and intracellular expression of cytotoxic T-lymphocyte antigen (CTLA)-4 molecules, and blocking of the CTLA-4 pathway restored the T-cell proliferation up to 70%, indicating an important role of the CTLA-4 molecule in the suppressor activity of anergic T cells. Taken together, our experiments demonstrate that anergic T cells induced by IL-10-treated DCs are able to suppress activation and function of T cells in an antigen-specific manner. Induction of anergic T cells might be exploited therapeutically for suppression of cellular immune responses in allergic or autoimmune diseases with identified (auto) antigens. FAU - Steinbrink, Kerstin AU - Steinbrink K AD - Department of Dermatology, University of Mainz, Langenbeckstrasse 1, D-551312 Mainz, Germany. steinbrink@hautklinik.klinik.uni-mainz.de FAU - Graulich, Edith AU - Graulich E FAU - Kubsch, Sebastian AU - Kubsch S FAU - Knop, Jurgen AU - Knop J FAU - Enk, Alexander H AU - Enk AH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation) RN - 0 (Antigens, Neoplasm) RN - 0 (CD4 Antigens) RN - 0 (CTLA-4 Antigen) RN - 0 (CTLA4 protein, human) RN - 0 (Immunoconjugates) RN - 0 (Isoantigens) RN - 130068-27-8 (Interleukin-10) RN - 7D0YB67S97 (Abatacept) RN - EC 1.14.18.1 (Monophenol Monooxygenase) SB - IM MH - Abatacept MH - Antigen-Presenting Cells/immunology MH - Antigens, CD MH - Antigens, Differentiation/immunology MH - Antigens, Neoplasm/analysis MH - CD4 Antigens/analysis MH - CD4-Positive T-Lymphocytes/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - CTLA-4 Antigen MH - Cell Division/drug effects MH - Cells, Cultured MH - Clonal Anergy/*immunology MH - Coculture Techniques MH - Dendritic Cells/cytology/drug effects/*immunology MH - Humans MH - *Immunoconjugates MH - Immunosuppression Therapy MH - Interleukin-10/*pharmacology MH - Isoantigens/immunology MH - Leukapheresis MH - Leukocytes, Mononuclear/cytology/immunology MH - Lymphocyte Activation MH - Melanoma/immunology MH - Monophenol Monooxygenase/analysis MH - T-Lymphocytes, Regulatory/immunology EDAT- 2002/03/16 10:00 MHDA- 2002/05/03 10:01 CRDT- 2002/03/16 10:00 PHST- 2002/03/16 10:00 [pubmed] PHST- 2002/05/03 10:01 [medline] PHST- 2002/03/16 10:00 [entrez] AID - S0006-4971(20)38034-4 [pii] AID - 10.1182/blood.v99.7.2468 [doi] PST - ppublish SO - Blood. 2002 Apr 1;99(7):2468-76. doi: 10.1182/blood.v99.7.2468.