The Neonatal CD8+ T Cell Repertoire Rapidly Diversifies during Persistent Viral Infection

Venturi, Vanessa; Nzingha, Kito; Amos, Timothy G.; Charles, Wisler; Dekhtiarenko, Iryna; Čičin-Šain, Luka; Davenport, Miles P.; Rudd, Brian D.

doi:10.4049/jimmunol.1501867

Cited by 17 publications

(12 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD8 + cell function in neonates has been mostly studied in response to infection with viruses, including influenza virus (25, 26), herpes simplex virus (27–29), respiratory syncytial virus (30), cytomegalovirus (31, 32), lymphocytic choriomeningitis virus (33), adenovirus (34), and Cas-Br-E murine leukemia virus (35–37). Most often, these viruses have been introduced either systemically or through a pulmonary route.…”

Section: Discussionmentioning

confidence: 99%

Rapid CD8+ Function Is Critical for Protection of Neonatal Mice from an Extracellular Bacterial Enteropathogen

Siefker

Adkins

2017

Front. Pediatr.

View full text Add to dashboard Cite

Both human and murine neonates are characteristically highly susceptible to bacterial infections. However, we recently discovered that neonatal mice are surprisingly highly resistant to oral infection with Yersinia enterocolitica. This resistance was linked with activation of both innate and adaptive responses, involving innate phagocytes, CD4+ cells, and B cells. We have now extended these studies and found that CD8+ cells also contribute importantly to neonatal protection from Y. enterocolitica. Strikingly, neonatal CD8+ cells in the mesenteric lymph nodes (MLN) are rapidly mobilized, increasing in proportion, number, and IFNγ production as early as 48 h post infection. This early activation appears to be critical for protection since B2m−/− neonates are significantly more susceptible than wt neonates to primary Y. enterocolitica infection. In the absence of CD8+ cells, Y. enterocolitica rapidly disseminated to peripheral tissues. Within 48 h of infection, both the spleens and livers of B2m−/−, but not wt, neonates became heavily colonized, likely leading to their deaths from sepsis. In contrast to primary infection, CD8+ cells were dispensable for the generation of immunological memory protective against secondary infection. These results indicate that CD8+ cells in the neonatal MLN contribute importantly to protection against an extracellular bacterial enteropathogen but, notably, they appear to act during the early innate phase of the immune response.

show abstract

Section: Discussionmentioning

confidence: 99%

Rapid CD8+ Function Is Critical for Protection of Neonatal Mice from an Extracellular Bacterial Enteropathogen

Siefker

Adkins

2017

Front. Pediatr.

View full text Add to dashboard Cite

show abstract

“…As such, the immunodominance of mucosal T RM against CMV changes with time, favoring the TCR repertoire that remains high in circulation ( 91 ). T RM have also been found in brain tissue after murine CMV infection ( 94 – 96 ). In the brain, CMV-specific T RM formation seems to be dependent on regulatory T cell (T reg ) activity.…”

Section: Cytomegalovirus (Cmv)mentioning

confidence: 99%

A Systematic Review: The Role of Resident Memory T Cells in Infectious Diseases and Their Relevance for Vaccine Development

et al. 2018

View full text Add to dashboard Cite

BackgroundResident memory T cells have emerged as key players in the immune response generated against a number of pathogens. Their ability to take residence in non-lymphoid peripheral tissues allows for the rapid deployment of secondary effector responses at the site of pathogen entry. This ability to provide enhanced regional immunity has gathered much attention, with the generation of resident memory T cells being the goal of many novel vaccines.ObjectivesThis review aimed to systematically analyze published literature investigating the role of resident memory T cells in human infectious diseases. Known effector responses mounted by these cells are summarized and key strategies that are potentially influential in the rational design of resident memory T cell inducing vaccines have also been highlighted.MethodsA Boolean search was applied to Medline, SCOPUS, and Web of Science. Studies that investigated the effector response generated by resident memory T cells and/or evaluated strategies for inducing these cells were included irrespective of published date. Studies must have utilized an established technique for identifying resident memory T cells such as T cell phenotyping.ResultsWhile over 600 publications were revealed by the search, 147 articles were eligible for inclusion. The reference lists of included articles were also screened for other eligible publications. This resulted in the inclusion of publications that studied resident memory T cells in the context of over 25 human pathogens. The vast majority of studies were conducted in mouse models and demonstrated that resident memory T cells mount protective immune responses.ConclusionAlthough the role resident memory T cells play in providing immunity varies depending on the pathogen and anatomical location they resided in, the evidence overall suggests that these cells are vital for the timely and optimal protection against a number of infectious diseases. The induction of resident memory T cells should be further investigated and seriously considered when designing new vaccines.

show abstract

“…8,53,54 A diverse TCR repertoire is closely linked to the required clonal complexity of the T-cell response against specific viral components. 55 Neonatal mice have diminished CTL responses to both dominant and subdominant epitopes for influenza virus 56 [58][59][60] As human fetal gestational age increases, the CDR3 length increases. 61,62 Rechavi and colleagues interrogated the total T-cell repertoire by next generation sequencing in a small number of fetal samples from selective fetal reduction cases, 12-26 weeks gestation, compared to children aged 9-48 months.…”

Section: An Important Component Of the Apc And T-cell Interaction Is Atmentioning

confidence: 99%

Dissecting the defects in the neonatal CD8+ T-cell response

Fike

Kumova

Carey

2019

Journal of Leukocyte Biology

View full text Add to dashboard Cite

The neonatal period presents a complex scenario where the threshold of reactivity toward colonizing microbiota, maternal antigens, autoantigens, and pathogens must be carefully moderated and balanced. CD8+ T cells are critical for the response against intracellular bacteria and viruses, but this immune compartment maintains altered function relative to adult counterparts because of the unique challenges which infants face. Here, we review our current understanding of the factors which may promote the attenuation and altered function of the neonatal CD8+ T‐cell response and potential avenues for future study. Specifically, we have focused on the neonatal CD8+ T‐cell ontogeny, memory formation, TCR structure and repertoire, TCR inhibitory receptors, and the clinical implications of altered neonatal CD8+ T‐cell function. Special emphasis has been placed on examining the response of preterm neonates relative to term neonates and adults.

show abstract

The Neonatal CD8+ T Cell Repertoire Rapidly Diversifies during Persistent Viral Infection

Cited by 17 publications

References 45 publications

Rapid CD8+ Function Is Critical for Protection of Neonatal Mice from an Extracellular Bacterial Enteropathogen

Rapid CD8+ Function Is Critical for Protection of Neonatal Mice from an Extracellular Bacterial Enteropathogen

A Systematic Review: The Role of Resident Memory T Cells in Infectious Diseases and Their Relevance for Vaccine Development

Dissecting the defects in the neonatal CD8+ T-cell response

Contact Info

Product

Resources

About