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Accelerate lung repair in SARS-CoV-2 pneumonia is essential for pandemic handling. Innate lymphoid cells (ILCs) are likely players, given their role in mucosal protection and tissue homeostasis. We studied ILC subpopulations at two time points in a cohort of patients admitted in the hospital due to SARS-CoV-2 infection. COVID-19 patients with moderate/severe respiratory failure featured profound depletion of circulating ILCs at hospital admission, in agreement with overall lymphocyte depletion. However, ILCs recovered in direct correlation with lung function improvement as measured by oxygenation index and in negative association with inflammatory and lung/endothelial damage markers like RAGE. While both ILC1 and ILC2 expanded, ILC2 showed the most striking phenotype changes, with CCR10 upregulation in strong correlation with these parameters. Overall, CCR10 + ILC2 emerge as relevant contributors to SARS-CoV-2 pneumonia recovery., (© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Treg cells, best identified by the expression of the transcription factor FOXP3, play a crucial role in maintaining self-tolerance. Natural Treg cells constitute an independent thymus-derived T-cell lineage whose developmental program in humans is still ill-defined. Here, we provide evidence of a Treg-cell differentiation pathway at the double positive (DP) stage, prior to commitment to the CD4(+) or CD8(+) lineage, in pediatric thymuses. FOXP3(+) DP cells displayed a functional IL-7 receptor and increased Bcl-2 levels that may protect them from cell death/negative selection, and an activated/suppressive phenotype that was lost as CD4 single positive (SP) cells matured and acquired egress markers. A subpopulation of FOXP3(+) DP thymocytes expressing CD103 likely represents the precursor of FOXP3(+) CD8SP cells, which homogeneously expressed this mucosal-homing molecule. Finally, co-cultures of DP thymocytes with primary thymic epithelial cells and multiple linear regression analyses support that FOXP3(+) SP cells are largely derived from FOXP3(+) DP thymocytes. Overall, our data suggest that human Treg-cell lineage commitment significantly occurs at the DP stage with possible implications for the diversity and autoreactivity of the natural Treg-cell repertoire., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

HIV-2 is associated with an attenuated form of HIV disease. We investigate here the immunosuppressive effects of the HIV-2 envelope protein, gp105. We found that gp105 suppresses activation of T cells through a monocyte-mediated mechanism. Suppression of T cell activation by gp105 depends on contact between monocytes and T cells, but not on CD4+CD25+ T cells. The TLR4 pathway is likely involved, since gp105 activates TLR4 signaling and induces TNF-alpha production by monocytes. Immunosuppression is viewed as the main pathophysiologic consequence of infection by HIV. However, the main immunologic defect caused by HIV, depletion of T cells, requires T cell activation. Our findings are consistent with a new concept that HIV-2 envelope proteins act on monocytes to suppress T cell activation and that this property may contribute to the benign course of HIV-2. We hypothesize that the HIV-2 envelope immunosuppressive properties limit bursts of T cell activation, thus reducing viremia and contributing to the slow rate of disease progression that characterizes HIV-2 disease.