Programmed Death 1 and Cytokine Inducible SH2-Containing Protein Dependent Expansion of Regulatory T Cells Upon Stimulation With Mycobacterium tuberculosis
| Autor: | Rohan Dhiman, Sivakumar Periasamy, Ramakrishna Vankayalapati, Amy R. Tvinnereim, Vijaya Lakshmi Valluri, Peter F. Barnes, Anuradha Bandaru, Padmaja Paidipally |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_treatment
Apoptosis Suppressor of Cytokine Signaling Proteins chemical and pharmacologic phenomena Biology T-Lymphocytes Regulatory Major Articles and Brief Reports Antigens CD Interferon medicine Humans Tuberculosis Immunology and Allergy IL-2 receptor CISH Lipoarabinomannan FOXP3 hemic and immune systems Mycobacterium tuberculosis Molecular biology Immunity Innate Interleukin 10 Infectious Diseases Cytokine Apoptosis Regulatory Proteins CD8 medicine.drug |
| Zdroj: | The Journal of Infectious Diseases. 203:1256-1263 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jir011 |
| Popis: | We previously found that CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) expand in response to Mycobacterium tuberculosis infection in individuals who are healthy tuberculin reactors, but not in tuberculin-negative individuals. We also found that the M. tuberculosis mannose-capped lipoarabinomannan and prostaglandin E2 produced by monocytes are involved in Treg expansion. In this study, we found that Tregs expanded from CD4(+)CCR4(+) cells but not from CCR4(-) cells. However, introduction of CCR4 small interfering RNA (siRNA) into CD4(+) cells only marginally reduced expansion of Tregs. Using siRNA and neutralizing antibodies, we found that expansion of Tregs by M. tuberculosis required expression of programmed death1 (PD-1) and expression of the signaling molecule, cytokine inducible SH2-containing protein (CISH). Anti-PD-1 siRNA inhibited expression of CISH by expanded Tregs. M. tuberculosis-expanded Tregs produced transforming growth factor β and interleukin 10 and reduced the frequency of interferon γ-producing autologous CD8(+) cells. We conclude that M. tuberculosis infection induces development of Tregs from CCR4(+) cells through a process that depends on PD-1and CISH. |
| Databáze: | OpenAIRE |
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