Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients
| Autor: | Laurence Weiss, Laure Caccavelli, Michèle Balbo, Yves Levy, Cédric Carbonneil, Vladimira Donkova-Petrini |
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| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
Immunology HIV Infections Biology Biochemistry CCL5 Immunophenotyping Interleukin 21 Epitopes Transforming Growth Factor beta Antiretroviral Therapy Highly Active Cytotoxic T cell Humans IL-2 receptor Antigen-presenting cell Interleukin 3 virus diseases Receptors Interleukin-2 Cell Biology Hematology Natural killer T cell Molecular biology Interleukin-10 CD4 Antigens Interleukin 12 Cell Division |
| Zdroj: | Blood. 104(10) |
| ISSN: | 0006-4971 |
| Popis: | The present study demonstrates that CD4+CD25+ T cells, expanded in peripheral blood of HIV-infected patients receiving highly active antiretroviral therapy (HAART), exhibit phenotypic, molecular, and functional characteristics of regulatory T cells. The majority of peripheral CD4+CD25+ T cells from HIV-infected patients expressed a memory phenotype. They were found to constitutively express transcription factor forkhead box P3 (Foxp3) messengers. CD4+CD25+ T cells weakly proliferated to immobilized anti-CD3 monoclonal antibody (mAb) and addition of soluble anti-CD28 mAb significantly increased proliferation. In contrast to CD4+CD25– T cells, CD4+CD25+ T cells from HIV-infected patients did not proliferate in response to recall antigens and to p24 protein. The proliferative capacity of CD4 T cells to tuberculin, cytomegalovirus (CMV), and p24 significantly increased following depletion of CD4+CD25+ T cells. Furthermore, addition of increasing numbers of CD4+CD25+ T cells resulted in a dose-dependent inhibition of CD4+CD25– T-cell proliferation to tuberculin and p24. CD4+CD25+ T cells responded specifically to p24 antigen stimulation by expressing transforming growth factor β (TGF-β) and interleukin 10 (IL-10), thus indicating the presence of p24-specific CD4+ T cells among the CD4+CD25+ T-cell subset. Suppressive activity was not dependent on the secretion of TGF-β or IL-10. Taken together, our results suggest that persistence of HIV antigens might trigger the expansion of CD4+CD25+ regulatory T cells, which might induce a tolerance to HIV in vivo. |
| Databáze: | OpenAIRE |
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