Level of double negative T cells, which produce TGF-β and IL-10, predicts CD8 T-cell activation in primary HIV-1 infection

Autor: Laurence Weiss, Michaela Müller-Trutwin, Maria Elena Manea, Céline Didier, Gaël Petitjean, Anne-Sophie Liovat, Daniel Scott-Algara, Feriel Tibaoui, Pierre-Marie Girard, Laurence Meyer, Françoise Barré-Sinoussi, Mathieu F. Chevalier, Pauline Campa
Přispěvatelé: Régulation des Infections Rétrovirales, Institut Pasteur [Paris] (IP), Université Paris Diderot - Paris 7 (UPD7), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), This work was supported by the ANRS and the Assistance Publique – Hôpitaux de Paris (AP-HP, Paris)., Institut Pasteur [Paris], Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Saint-Antoine [APHP]
Jazyk: angličtina
Rok vydání: 2012
Předmět:
CD4-Positive T-Lymphocytes
Male
medicine.medical_treatment
HIV Infections
CD38
CD8-Positive T-Lymphocytes
Lymphocyte Activation
T-Lymphocytes
Regulatory

MESH: HIV Infections/pathology
MESH: Lymphocyte Activation*/genetics
0302 clinical medicine
Transforming Growth Factor beta
Immunology and Allergy
Cytotoxic T cell
MESH: HIV Infections/genetics
IL-2 receptor
Longitudinal Studies
Prospective Studies
MESH: Longitudinal Studies
0303 health sciences
MESH: T-Lymphocytes
Regulatory/immunology

Chemistry
FOXP3
Forkhead Transcription Factors
3. Good health
Interleukin-10
Interleukin 10
Infectious Diseases
Cytokine
MESH: CD8-Positive T-Lymphocytes/immunology
[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology
Disease Progression
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
MESH: Disease Progression
France
MESH: Immunophenotyping
Immunology
MESH: Forkhead Transcription Factors/immunology
Immunophenotyping
MESH: CD4-Positive T-Lymphocytes/immunology
03 medical and health sciences
medicine
Humans
MESH: Interleukin-10/metabolism
Interleukin-7 receptor
030304 developmental biology
MESH: HIV-1/immunology
MESH: Humans
MESH: HIV Infections/immunology
MESH: Male
MESH: Prospective Studies
MESH: France
HIV-1
MESH: Female
CD8
MESH: Transforming Growth Factor beta/metabolism
030215 immunology
Zdroj: AIDS. Official journal of the international AIDS Society
AIDS. Official journal of the international AIDS Society, 2012, 26 (2), pp.139-148. ⟨10.1097/QAD.0b013e32834e1484⟩
AIDS
AIDS, Lippincott, Williams & Wilkins, 2012, 26 (2), pp.139-148. ⟨10.1097/QAD.0b013e32834e1484⟩
ISSN: 0269-9370
1473-5571
DOI: 10.1097/QAD.0b013e32834e1484⟩
Popis: International audience; OBJECTIVE:Persistent immune activation plays a central role in the pathogenesis of HIV disease. Besides natural regulatory T cells (nTregs), 'double negative' T cells shown to exhibit regulatory properties could be involved in the control of harmful immune activation. The aim of this study was to analyze, in patients with primary HIV infection (PHI), the relationship between CD4(+)CD25(+)CD127(low)FoxP3(+) nTregs or CD3(+)CD4(-)CD8(-) double negative T cells and systemic immune activation.DESIGN:A prospective longitudinal study of patients with early PHI.METHODS:Twenty-five patients were included. Relationships between frequency of Treg subsets and T-cell activation, assessed on fresh peripheral blood mononuclear cells, were analyzed using nonparametric tests. Cytokine production by double negative T cells was assessed following anti-CD3/anti-CD28 stimulation.RESULTS:No relationship was found between T-cell activation and frequencies of nTregs. In contrast, a strong negative relationship was found at baseline between the proportion of double negative T cells and the proportion of activated CD8 T cells coexpressing CD38 and HLA-DR (P = 0.005) or expressing Ki-67 (P = 0.002). In addition, the frequency of double negative T cells at baseline negatively correlated with the frequency of HLA-DR(+)CD38(+)CD8(+) T cells at month 6, defining the immune activation set point (P = 0.031). High proportions of stimulated double negative T cells were found to produce the immunosuppressive cytokines transforming growth factor-β1 and/or IL-10.CONCLUSION:The proportion of double negative T cells at baseline was found to be predictive of the immune activation set point. Our data strongly suggest that double negative T cells may control immune activation in PHI. This effect might be mediated through the production of TGF-β1/IL-10 known to downmodulate immune activation.
Databáze: OpenAIRE