TCR ζ down-regulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organs
| Autor: | Amal Halabi, Michal Baniyash, Efrat Manaster, Ofer Levy, Analía V. Ezernitchi, Eli Pikarsky, Ilan Vaknin, Lior Shapira, Leonor Cohen-Daniel |
|---|---|
| Předmět: |
Myeloid
Lymphoid Tissue medicine.medical_treatment T cell T-Lymphocytes Immunology Receptors Antigen T-Cell Down-Regulation Macrophage-1 Antigen Inflammation Biology Immune tolerance Mice medicine Immune Tolerance Immunology and Allergy Animals Myeloid Cells Mice Inbred BALB C Immunosuppression Immunotherapy Flow Cytometry medicine.anatomical_structure Lymphatic system Chronic Disease Female Bone marrow medicine.symptom |
| Zdroj: | Scopus-Elsevier |
| Popis: | T cell AgR ζ chain down-regulation associated with T cell dysfunction has been described in cancer, infectious, and autoimmune diseases. We have previously shown that chronic inflammation is mandatory for the induction of an immunosuppressive environment leading to this phenomenon. To identify the key immunosuppressive components, we used an in vivo mouse model exhibiting chronic inflammation-induced immunosuppression. Herein, we demonstrate that: 1) under chronic inflammation secondary lymphatic organs display various immunological milieus; ζ chain down-regulation and T cell dysfunction are induced in the spleen, peripheral blood, and bone marrow, but not in lymph nodes, correlating with elevated levels of Gr1+Mac-1+ myeloid suppressor cells (MSC); 2) MSC are responsible for the induction of such an immunosuppression under both normal and inflammatory conditions; and 3) normal T cells administered into mice exhibiting an immunosuppressive environment down-regulate their ζ expression. Such an environment is anticipated to limit the success of immunotherapeutic strategies based on vaccination and T cell transfer, which are currently under investigation for immunotherapy of cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|