Heterogeneity of human anti-viral immunity shaped by virus, tissue, age, and sex

Abstract

The persistence of anti-viral immunity is essential for protection and exhibits profound heterogeneity across individuals. Here, we elucidate the factors that shape maintenance and function of anti-viral T cell immunity in the body by comprehensive profiling of virus-specific T cells across blood, lymphoid organs, and mucosal tissues of organ donors. We use flow cytometry, T cell receptor sequencing, single-cell transcriptomics, and cytokine analysis to profile virus-specific CD8 + T cells recognizing the ubiquitous pathogens influenza and cytomegalovirus. Our results reveal that virus specificity determines overall magnitude, tissue distribution, differentiation, and clonal repertoire of virus-specific T cells. Age and sex influence T cell differentiation and dissemination in tissues, while T cell tissue residence and functionality are highly correlated with the site. Together, our results demonstrate how the covariates of virus, tissue, age, and sex impact the anti-viral immune response, which is important for targeting, monitoring, and predicting immune responses to existing and emerging viruses.

Early and Polyantigenic CD4 T Cell Responses Correlate with Mild Disease in Acute COVID-19 Donors

“…SARS-CoV-2 T cell reactivity is influenced by factors such as sex and age [16,17]. As mentioned above, the mild, moderate, and severe disease categories had similar representations of male and female sexes (Figure 1).…”

Immunological memory to SARS‐CoV‐2 infection and COVID‐19 vaccines

“…Human antiviral immune memory may be influenced by variables such as viral factors related to the infection event such as viral dose and tissue distribution, and host factors such as age, sex, and general health of the host. 126 A distinctive feature of SARS‐CoV‐2 infection and COVID‐19 disease is the wide range of clinical outcomes, ranging from fully asymptomatic infection to severe disease and death. The heterogeneity in clinical outcomes associated with SARS‐CoV‐2 infection and COVID‐19 disease is paralleled by large variations in heterogeneity at the level of CD4 T cell responses.…”

Divide and Conquer: Phenotypic and Temporal Heterogeneity Within CD8+ T Cell Responses

“…High-dimensional single-cell measurements and fate-mapping techniques have been instrumental in revealing low-frequency but functionally important precursor cells that emerge during the early proliferative period [exemplified by (15)(16)(17)]. Beyond canonical differentiation pathways, single-cell transcriptomic studies of T cells from different anatomical locations, such as (18,19), have demonstrated tissue-associated variation in gene expression within nominal subsets. Thus, T cell differentiation is a highly complex, diverging process.…”