||Immune Function and Dysfunction
Oral Abstract Session : Track A
||Session Room 7
||23.07.2012, 16:30 - 18:00
Jean-Pierre Routy, Canada
Barbara. L. Shacklett, United States
|HIV controllers maintain a population of highly efficient Th1 effector cells in spite of persistently low viral antigenemia|
B. Vingert1, D. Benati1, O. Lambotte2, P. de Truchis3, L. Slama4, P. Jeannin1, S. Perez-Patrigeon1, F. Boufassa5, W.W. Kwok6, F. Lemaître7, J.-F. Delfraissy2, J. Thèze1, L.A. Chakrabarti1
1Institut Pasteur, Unité d'Immunogénétique Cellulaire, Paris, France, 2INSERM U802, Bicêtre Hospital, Le Kremlin-Bicêtre, France, 3AP-HP, Department of Infectious and Tropical Diseases, Raymond Poincaré Hospital, Garches, France, 4AP-HP, Department of Infectious and Tropical Diseases, Tenon Hospital, Paris, France, 5INSERM U822, Bicêtre Hospital, Le Kremlin-Bicêtre, France, 6Benaroya Research Institute at Virginia Mason, Seattle, United States, 7Unité de Dynamiques des Réponses Immunes and INSERM U668, Institut Pasteur, Paris, France
L. Chakrabarti, France
|The majority of freshly sorted SIV-specific CD8+ T cells cannot suppress viral replication in SIV-infected macrophages|
L. Vojnov1, M. Martins1, A. Bean1, M. Veloso de Santana2, J. Sacha3, N. Wilson1, M. Bonaldo4, R. Galler4, M. Stevenson5, D. Watkins5
1University of Wisconsin-Madison, Madison, United States, 2Instituto Oswaldo Cruz-FIOCRUZ, Rio de Janeiro, Brazil, 3Oregon Health and Science University, Beaverton, United States, 4Fundação Oswaldo Cruz, Rio de Janeiro, Brazil, 5University of Miami Miller School of Medicine, Miami, United States
L. Vojnov, Liberia
|HIV-1 peptide-specific NK cell responses in HIV seropositive and highly exposed seronegative men|
R. Fecek, R. Mailliard, C. Rinaldo
University of Pittsburgh Graduate School of Public Health, Infectious Diseases and Microbiology, Pittsburgh, United States
R. Fecek, United States
|Natural control of HIV infection is associated with an isotype switched IgG antibody response to HIV core antigens in patients with 'non-protective' HLA-B alleles|
M. French1, R. Center2, K. Wilson3, I. Fleyfel1, S. Fernandez1, A. Kelleher4
1University of Western Australia, School of Pathology and Laboratory Medicine, Perth, Australia, 2University of Melbourne, Microbiology and Immunology, Melbourne, Australia, 3National Serology Reference Laboratory, Melbourne, Australia, 4University of New South Wales, Kirby Institute, Sydney, Australia
M. French, Australia
|IL-7 suppresses transcription of the IL-7 receptor alpha (CD127) gene in human CD8 T cells by inducing the expression of a STAT5-dependent transcriptional repressor|
F. Al-Ghazawi1,2, E. Faller1,2, P. Parmar1,2, J. Kakal1, P. MacPherson1,2,3
1University of Ottawa, Biochemistry, Microbiology and Immunology, Ottawa, Canada, 2Ottawa Hospital Research Institute, Chronic and Infectious Diseases, Ottawa, Canada, 3Ottawa Hospital, Ottawa, Canada
F. Al-Ghazawi, Canada
|HIV controllers maintain a population of highly efficient Th1 effector cells in spite of persistently low viral antigenemia - Lisa A. Chakrabarti|
|The majority of freshly sorted SIV-specific CD8+ T cells cannot suppress viral replication in SIV-infected macrophages - Lara Vojnov|
|Natural control of HIV infection is associated with an isotype switched IgG antibody response to HIV core antigens in patients with 'non-protective' HLA-B alleles - Martyn French|
Track A report by Irene Onyango
The degree of immune dysfunction during HIV infection shows considerable inter-individual variability. CD4 T cells, which are the main target for HIV infection, were tested against three peptides. HIV controllers were found to have highly efficient Th1 effectors, which may contribute to viral control.
It is known that SIV/HIV can infect macrophages, but the role of macrophages as HIV/SIV reservoir has not being determined. The study suggested that macrophages may be an important reservoir for SIV, hence difficulties for specific CD8+ T cells to fully suppress viral replication.
Highly exposed seronegative (HESN) are individuals who remain uninfected even after repeated exposure to HIV. Natural Killer (NK) cells are known to play a key role in immune response against viral infection by recognizing and killing infected cells. In depth assessment of HIV-specific NK responses in HESN was performed. In a subset of the HESN study population, NK cells exhibit HIV-1 specific responses. Whether those merely reflect exposure to HIV-1 antigens or are actually involved in protection against HIV acquisition remain to be determined.
Immune control in HIV-infected individuals able to maintain low viremia in absence of antiretroviral therapy (controllers) notably consists in CD8+ T cell responses to HIV core antigens, encoded by Gag, restricted by 'protective' HLA-B alleles. Slow progression can also be associated with antibodies against HIV core proteins, but mechanisms are unclear. A number of cytokines implicated in isotype switching were investigated. An isotype switched IgG antibody response to HIV core antigens associated with better control of HIV infection in patients without known protective HLA-B alleles.
IL-7 plays an important role in T-cell survival, homeostasis and function. Given the importance of IL-7 in HIV pathogenesis, there is need to understand how does IL-7 regulate the expression of its own receptor CD127. The study showed that IL-7 suppresses CD127 gene transcription in human CD8 T-cells, resulting in dysregulation of the IL-7 signaling cascade in HIV infection.