Aging of lymphoid stromal architecture impacts immune responses

Lancaster, Jessica N.

doi:10.1016/j.smim.2023.101817

Cited by 2 publications

(1 citation statement)

References 120 publications

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“…More recently, it was demonstrated that Tfh cells have aberrant expression of CXCR4, which repositions them to the dark zone of the GC and impairs differentiation of follicular dendritic cells, contributing to diminished GC B cell expansion (Silva‐Cayetano et al., 2023 ). Age‐associated changes to lymph node stromal architecture has been described (Lancaster, 2023 ), and our previous work, using live‐cell 2‐photon imaging, found that naïve T cell motility was impaired within regions of accumulated fibrosis within the aged lymph nodes (Kwok et al., 2022 ). We hypothesize that our observations of decreased PD‐1 and CD40L are also indicative of imprecise spatial positioning of Tfh, which diminishes the efficiency of GC B cell interactions within the aged tissue microenvironment.…”

Section: Discussionmentioning

confidence: 87%

The aged microenvironment impairs BCL6 and CD40L induction in CD4⁺ T follicular helper cell differentiation

Fisher,

Adán‐Barrientos,

Kumar

et al. 2024

Aging Cell

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Weakened germinal center responses by the aged immune system result in diminished immunity against pathogens and reduced efficacy of vaccines. Prolonged contacts between activated B cells and CD4+ T cells are crucial to germinal center formation and T follicular helper cell (Tfh) differentiation, but it is unclear how aging impacts the quality of this interaction. Peptide immunization confirmed that aged mice have decreased expansion of antigen‐specific germinal center B cells and reduced antibody titers. Furthermore, aging was associated with accumulated Tfh cells, even in naïve mice. Despite increased numbers, aged Tfh had reduced expression of master transcription factor BCL6 and increased expression of the ectonucleotidase CD39. In vitro activation revealed that proliferative capacity was maintained in aged CD4+ T cells, but not the costimulatory molecule CD40L. When activated in vitro by aged antigen‐presenting cells, young CD4+ naïve T cells generated reduced numbers of activated cells with upregulated CD40L. To determine the contribution of cell‐extrinsic influences on antigen‐specific Tfh induction, young, antigen‐specific B and CD4+ T cells were adoptively transferred into aged hosts prior to peptide immunization. Transferred cells had reduced expansion and differentiation into germinal center B cell and Tfh and reduced antigen‐specific antibody titers when compared to young hosts. Young CD4+ T cells transferred aged hosts differentiated into Tfh cells with reduced PD‐1 and BCL6 expression, and increased CD39 expression, though they maintained their mitochondrial capacity. These results highlight the role of the lymphoid microenvironment in modulating CD4+ T cell differentiation, which contributes to impaired establishment and maintenance of germinal centers.

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Section: Discussionmentioning

confidence: 87%

The aged microenvironment impairs BCL6 and CD40L induction in CD4⁺ T follicular helper cell differentiation

Fisher,

Adán‐Barrientos,

Kumar

et al. 2024

Aging Cell

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Poly I:C vaccination drives transient CXCL9 expression near B cell follicles in the lymph node through type-I and type-II interferon signaling

Ball,

Morgaenko,

Anbaei

et al. 2024

Cytokine

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Aging of lymphoid stromal architecture impacts immune responses

Cited by 2 publications

References 120 publications

The aged microenvironment impairs BCL6 and CD40L induction in CD4⁺ T follicular helper cell differentiation

The aged microenvironment impairs BCL6 and CD40L induction in CD4⁺ T follicular helper cell differentiation

Poly I:C vaccination drives transient CXCL9 expression near B cell follicles in the lymph node through type-I and type-II interferon signaling

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Aging of lymphoid stromal architecture impacts immune responses

Cited by 2 publications

References 120 publications

The aged microenvironment impairs BCL6 and CD40L induction in CD4+ T follicular helper cell differentiation

The aged microenvironment impairs BCL6 and CD40L induction in CD4+ T follicular helper cell differentiation

Poly I:C vaccination drives transient CXCL9 expression near B cell follicles in the lymph node through type-I and type-II interferon signaling

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Product

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The aged microenvironment impairs BCL6 and CD40L induction in CD4⁺ T follicular helper cell differentiation

The aged microenvironment impairs BCL6 and CD40L induction in CD4⁺ T follicular helper cell differentiation