Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8 T cells.

The molecular properties of CD8 T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8 T cells, obtained using a modified Antigen-Reactive T cell Enrichment (ARTE) assay, from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8 T cell response to SARS-CoV-2 was 'exhausted' or not.

Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4 T Cells in COVID-19.

The contribution of CD4 T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present single-cell transcriptomic analysis of >100,000 viral antigen-reactive CD4 T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper cells and cytotoxic T helper (T) cells (CD4-CTLs) responding to SARS-CoV-2 and reduced proportion of SARS-CoV-2-reactive regulatory T cells (T).

Single-Cell Transcriptomic Analysis of SARS-CoV-2 Reactive CD4 T Cells.

The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present large-scale single-cell transcriptomic analysis of viral antigen-reactive CD4+ T cells from 32 COVID-19 patients. In patients with severe disease compared to mild disease, we found increased proportions of cytotoxic follicular helper (T) cells and cytotoxic T helper cells (CD4-CTLs) responding to SARS-CoV-2, and reduced proportion of SARS-CoV-2 reactive regulatory T cells.

Severely ill COVID-19 patients display augmented functional properties in SARS-CoV-2-reactive CD8 T cells.

The molecular properties of CD8 T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8 T cells from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8 T cell response to SARS-CoV-2 was 'exhausted' or not.

Single-cell transcriptomic analysis of SARS-CoV-2 reactive CD4 T cells.

The contribution of CD4 T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present large-scale single-cell transcriptomic analysis of viral antigen-reactive CD4 T cells from 32 COVID-19 patients. In patients with severe disease compared to mild disease, we found increased proportions of cytotoxic follicular helper (T ) cells and cytotoxic T helper cells (CD4-CTLs) responding to SARS-CoV-2, and reduced proportion of SARS-CoV-2 reactive regulatory T cells.

The T-cell Response to Epstein-Barr Virus-New Tricks From an Old Dog.

Epstein-Barr virus (EBV) infects most people and establishes life-long infection controlled by the host's immune system. The genetic stability of the virus, deep understanding of the viral antigens and immune epitopes recognized by the host's T-cell system and the fact that recent infection can be identified by the development of symptomatic infectious mononucleosis makes EBV a powerful system in which to study human immunology. The association between EBV and multiple cancers also means that the lessons learned have strong translational potential.

Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4 T Cells.

CD4 T cells are essential for immune protection against viruses, yet their multiple roles remain ill-defined at the single-cell level in humans. Using HLA class II tetramers, we studied the functional properties and clonotypic architecture of EBV-specific CD4 T cells in patients with infectious mononucleosis, a symptomatic manifestation of primary EBV infection, and in long-term healthy carriers of EBV. We found that primary infection elicited oligoclonal expansions of T1-like EBV-specific CD4 T cells armed with cytotoxic proteins that responded immediately ex vivo to challenge with EBV-infected B cells.

CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles.

During unresolved infections, some viruses escape immunological control and establish a persistant reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (TFH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (TC cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (TFC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3.