Monocytic reactive oxygen species-induced T cell apoptosis impairs cellular immune response to SARS-CoV-2 mRNA vaccine.

Background: We have recently shown that, during acute severe COVID-19, SARS-CoV-2 spike protein (S) induces a cascade of events resulting in T cell apoptosis. Indeed, by neutralizing the protease activity of its receptor, ACE2, S induces an increase in circulating Angiotensin II (AngII), resulting in monocytic release of reactive oxygen species (ROS) and programmed T cell death.

Objective: Here, we tested whether SARS-CoV-2 mRNA vaccines, known to cause the circulation of the vaccine antigen, S-protein receptor binding domain (RBD), might trigger the same cascade.

Despite early antiretroviral therapy effector memory and follicular helper CD4 T cells are major reservoirs in visceral lymphoid tissues of SIV-infected macaques.

Whereas antiretroviral therapy (ART) suppresses viral replication, ART discontinuation results in viral rebound, indicating the presence of viral reservoirs (VRs) established within lymphoid tissues. Herein, by sorting CD4 T-cell subsets from the spleen, mesenteric and peripheral lymph nodes (LNs) of SIVmac251-infected rhesus macaques (RMs), we demonstrate that effector memory (TEM) and follicular helper (TFH) CD4 T cells harbor the highest frequency of viral DNA and RNA, as well of early R-U5 transcripts in ART-naïve RMs. Furthermore, our results highlight that these two CD4 T cells subsets harbor viral DNA and early R-U5 transcripts in the spleen and mesenteric LNs (but not in peripheral LN) of RMs treated with ART at day 4 post infection suggesting that these two anatomical sites are important for viral persistence.

Mucosal T follicular helper cells in SIV-infected rhesus macaques: contributing role of IL-27.

Mesenteric lymph nodes (MLNs), that drain the large and small intestine, are critical sites for the induction of oral tolerance. Although depletion of CD4 T cells in the intestinal lamina propria is a hallmark of HIV infection, CD4 T cell dynamics in MLNs is less known due to the lack of accessibility to these LNs. We demonstrate the early loss of memory CD4 T cells, including T follicular helper cells (Tfh) and a remodeling of MLN architecture in SIV-infected rhesus macaques (RMs).

Correction: Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

[This corrects the article DOI: 10.1371/journal.ppat.

Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques.

Follicular T helper cells (Tfh), a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs) during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs) during the acute phase of infection, which persists thereafter.