Increased Thymic Production of Naive Regulatory T-Cells Distinguish Patients with HAART-mediated control from those with spontaneous control of HIV Norma I. Rallón, Clara Restrepo, María Salgado, Carmen de Mendoza, Sara Lozano, Mariola López, Alejandra Peris, Vincent Soriano, and José M. Benito Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
Nature Immunology, 2005 BACKGROUND Treg cells are a subset of CD4+ T lymphocytes expressing Foxp3+
Teff Treg BACKGROUND Treg cells are a subset of CD4+ T lymphocytes expressing Foxp3+ Nature Immunology, 2005 Treg cells play a critical role in maintaining the delicate balance between preventing immunopathology and allowing the immune response to clear infections.
Teff Treg BACKGROUND Patients with HIV disease progression HIV suppressing virus-specific T-cell responses
The mechanism leading to increased Treg levels in HIV infection is unknown ? ?
BACKGROUND Patients with HIV control HAART-mediated control Spontaneous control ? ?
OBJECTIVES • 1. To examine the levels of Treg cells in different scenarios of HIV infection • HIV disease progression • Long-term successful HAART • Long-term non progression (LTNPs) • 2. To determine levels of naïve Tregs and the proportion of these cells recently emigrated from thymus.
PATIENTS AND METHODS • Treg cells: CD4+T-cells expressing Foxp3+
PATIENTS AND METHODS • Naïve-Treg cells CD4+ Foxp3+ [CD45RA+ CD27+] • Truly Naive Treg cells CD4+ Foxp3+ CD45RA+ CD27+ [CD31+] • Treg cells: CD4+T-cells expressing Foxp3+
Levels of Treg cells in the study population p=0.081 Treg cell p<0.0001 p=0.002 p<0.0001
Teff Treg Teff Treg Treg cell levels distinguish HAART-mediated from spontaneous control of HIV replication Patients with HIV control HAART-mediated control Spontaneous control
Levels of CD31 expression on Naïve Treg cells in the study population p=0.713 Thymicnaive Treg cell p=0.01 p<0.0001 p<0.0001
Origin of Naïve Treg cells in different scenarios Patients with HIV control HAART-mediated control Spontaneous control
CONCLUSIONS • Significant increased levels of Treg cells are maintained in patients with long-term suppressive HAART, most likely as a consequence of increased thymic output. • These findings support that Treg cells may still impair HIV-specific T-cell responses, even in the context of HAART-mediated virus suppression. • On the contrary, normal levels of both Treg cells and CD31+ on naïve Treg cells observed in LTNPs could contribute to the better control of HIV replication in these patients.
ACKNOWLEDGMENTS To all staff at the Molecular Biology Laboratory and clinicians from the Infectious Disease Department of the Hospital Carlos III, Madrid, Spain. NEAT European Project (LSHP-CT-2006- 037570)