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

Poon, Maya M.L.; Byington, Eve; Meng, Wenzhao; Kubota, Masaru; Matsumoto, Rei; Grifoni, Alba; Weiskopf, Daniela; Dogra, Pranay; Lam, Nora; Szabo, Peter A.; Ural, Basak Burcu; Wells, Steven B.; Rosenfeld, Aaron M.; Brusko, Todd M.; Brusko, Todd M.; Connors, Thomas J.; Sette, Alessandro; Sims, Peter A.; Prak, Eline T. Luning; Shen, Yufeng; Farber, Donna L.

doi:10.1016/j.celrep.2021.110071

Cited by 45 publications

(40 citation statements)

References 81 publications

(120 reference statements)

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“…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).…”

Section: Sex and Age In Relation To Cd4+ T Cell Responses In Acute Co...mentioning

confidence: 63%

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

Tarke

Potesta

Varchetta

et al. 2022

IJMS

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We assessed SARS-CoV-2-specific CD4+ and CD8+ T cell responses in samples from 89 acute COVID-19 patients, utilizing blood samples collected during the first wave of COVID-19 in Italy. The goal of the study was to examine correlations between SARS-CoV-2-specific T cell responses in the early phase comparing mild, moderate, or severe COVID-19 disease outcomes. T cell responses to the spike (S) and non-S proteins were measured in a combined activation-induced marker (AIM) and intracellular cytokine staining (ICS) assay. Early CD4+ T cell responses to SARS-CoV-2 S correlated with milder disease by both AIM and IFNγ ICS readouts. The correlation of S-specific CD4+ T cell responses with milder disease severity was most striking within the first two weeks of symptom onset compared to later time points. Furthermore, donors with milder disease were associated with polyantigenic CD4+ T cell responses that recognized more prominently non-S proteins in addition to S, while severe acute COVID-19 was characterized by lower magnitudes of CD4+ T cell responses and a narrower repertoire. In conclusion, this study highlights that both the magnitude and breadth of early SARS-CoV-2-specific CD4+ T cell responses correlated with milder disease outcomes in acute COVID-19 patients.

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Section: Sex and Age In Relation To Cd4+ T Cell Responses In Acute Co...mentioning

confidence: 63%

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

Tarke

Potesta

Varchetta

et al. 2022

IJMS

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“…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.…”

Section: Cd4 T Cell Memory To Sars‐cov ‐2mentioning

confidence: 99%

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

Sette

Crotty

2022

Immunological Reviews

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120

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Immunological memory is the basis of protective immunity provided by vaccines and previous infections. Immunological memory can develop from multiple branches of the adaptive immune system, including CD4 T cells, CD8 T cells, B cells, and long-lasting antibody responses. Extraordinary progress has been made in understanding memory to SARS-CoV-2 infection and COVID-19 vaccines, addressing development; quantitative and qualitative features of different cellular and anatomical compartments; and durability of each cellular component and antibodies. Given the sophistication of the measurements; the size of the human studies; the use of longitudinal samples and cross-sectional studies; and head-to-head comparisons between infection and vaccines or between multiple vaccines, the understanding of immune memory for one year to SARS-CoV-2 infection and vaccines already supersedes that of any other acute infectious disease. This knowledge may help inform public policies regarding COVID-19 and COVID-19 vaccines, as well as the scientific development of future vaccines against SARS-CoV-2 and other diseases.

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“…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.…”

Section: The Branching Tree Of Differentiationmentioning

confidence: 99%

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

Richard

2022

Front. Immunol.

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The advent of technologies that can characterize the phenotypes, functions and fates of individual cells has revealed extensive and often unexpected levels of diversity between cells that are nominally of the same subset. CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), are no exception. Investigations of individual CD8+ T cells both in vitro and in vivo have highlighted the heterogeneity of cellular responses at the levels of activation, differentiation and function. This review takes a broad perspective on the topic of heterogeneity, outlining different forms of variation that arise during a CD8+ T cell response. Specific attention is paid to the impact of T cell receptor (TCR) stimulation strength on heterogeneity. In particular, this review endeavors to highlight connections between variation at different cellular stages, presenting known mechanisms and key open questions about how variation between cells can arise and propagate.

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

Cited by 45 publications

References 81 publications

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

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

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

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

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