P-C1 Preservation of lymphopoietic potential and virus suppressive2 capacity by CD8+ T-cells in HIV-2 infected controllers

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HIV-2 infection represents a unique model of attenuated infection by a human immunodeficiency virus. Compared to HIV-1 infection, HIV-2 infection is characterized by slower CD4+ T cell count decline and disease progression in the absence of antiretroviral therapy. Although HIV-2 infected individuals are usually characterized by low viral load and immune activation levels, the underlying mechanisms remain poorly understood. A better understanding of HIV-2 pathogenesis is central to open new therapeutic avenues to establish natural control of HIV-1 replication in infected patients. Here, we studied the capacity of HIV-2 infected patients to support long term renewal of the CD8+ T cell lymphocyte compartment by preserving immune resources, including lymphoid progenitors and thymic activity, and the efficacy of effector CD8+ T cells to control the virus. Our findings suggest that preservation of the host immune resources supports the maintenance of a strong CD8+ T cell capacity to suppress HIV-2. This effective and durable antiviral response likely participates to establishing a virtuous circle, during which controlled viral replication permits the preservation of potent immune functions, and vice versa, thus preventing disease progression in HIV-2 infected patients. Owing to the maintenance of a strong lymphopoietic capacity in infected patients, T cell mediated immune responses appears to be better preserved in HIV-2 infection and can sustain a very effective suppression of viral replication over several years of chronic infection. HIV-2 specific CD8+ T cells display an early or young differentiated phenotype, potentially reflecting T cell renewal potential. Next, they habor particularly potent effector functions, highlighted by their exceptional capacity to suppress the virus in autologous CD4+ T cells. These CD8+ T cell characteristics are similar to those observed in HHIV-1 infected elite controllers in many aspects, and are likely to be both the cause and the consequence of this effective control of the virus.

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