tetano
Editor, Senior Moderator
Cell Rep
. 2025 Feb 3;44(2):115247.
doi: 10.1016/j.celrep.2025.115247. Online ahead of print. Repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain-resident memory CD8[SUP]+[/SUP] T cells
Madison R Mix[SUP] 1 [/SUP], Stephanie van de Wall[SUP] 2 [/SUP], Mohammad Heidarian[SUP] 3 [/SUP], Elizabeth A Escue[SUP] 3 [/SUP], Cori E Fain[SUP] 2 [/SUP], Lecia L Pewe[SUP] 2 [/SUP], Lisa S Hancox[SUP] 2 [/SUP], Sahaana A Arumugam[SUP] 1 [/SUP], Cassie M Sievers[SUP] 2 [/SUP], Vladimir P Badovinac[SUP] 4 [/SUP], John T Harty[SUP] 5 [/SUP]
Affiliations
The human brain harbors virus-specific, tissue-resident memory (T[SUB]RM[/SUB]) CD8[SUP]+[/SUP] T cells. However, the impact of repeated peripheral viral infection on the generation, phenotype, localization, and recall responses of brain T[SUB]RM[/SUB] remains elusive. Here, utilizing two murine models of peripheral viral infection, we demonstrate that circulating memory CD8[SUP]+[/SUP] T cells with previous antigen exposure exhibit a markedly reduced capacity to form brain T[SUB]RM[/SUB] compared to naive CD8[SUP]+[/SUP] T cells. Repetitively stimulated brain T[SUB]RM[/SUB] also demonstrate differential inhibitory receptor expression, preserved functionality, and divergent localization patterns compared to primary memory counterparts. Despite these differences, repetitively stimulated brain T[SUB]RM[/SUB] provide similar protection against intracranial infection as primary populations with superior recall-based recruitment of peripheral lymphocytes. As CD8[SUP]+[/SUP] T cells may distinctly seed the brain with each repeated infection of the same host, these findings point to heterogeneity in the brain T[SUB]RM[/SUB] pool that is dictated by prior peripheral antigen stimulation history.
Keywords: CP: Immunology; CP: Neuroscience; brain T(RM); influenza virus; neuroimmunology; repetitive antigen stimulation; viral infection.
. 2025 Feb 3;44(2):115247.
doi: 10.1016/j.celrep.2025.115247. Online ahead of print. Repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain-resident memory CD8[SUP]+[/SUP] T cells
Madison R Mix[SUP] 1 [/SUP], Stephanie van de Wall[SUP] 2 [/SUP], Mohammad Heidarian[SUP] 3 [/SUP], Elizabeth A Escue[SUP] 3 [/SUP], Cori E Fain[SUP] 2 [/SUP], Lecia L Pewe[SUP] 2 [/SUP], Lisa S Hancox[SUP] 2 [/SUP], Sahaana A Arumugam[SUP] 1 [/SUP], Cassie M Sievers[SUP] 2 [/SUP], Vladimir P Badovinac[SUP] 4 [/SUP], John T Harty[SUP] 5 [/SUP]
Affiliations
- PMID: 39903666
- DOI: 10.1016/j.celrep.2025.115247
The human brain harbors virus-specific, tissue-resident memory (T[SUB]RM[/SUB]) CD8[SUP]+[/SUP] T cells. However, the impact of repeated peripheral viral infection on the generation, phenotype, localization, and recall responses of brain T[SUB]RM[/SUB] remains elusive. Here, utilizing two murine models of peripheral viral infection, we demonstrate that circulating memory CD8[SUP]+[/SUP] T cells with previous antigen exposure exhibit a markedly reduced capacity to form brain T[SUB]RM[/SUB] compared to naive CD8[SUP]+[/SUP] T cells. Repetitively stimulated brain T[SUB]RM[/SUB] also demonstrate differential inhibitory receptor expression, preserved functionality, and divergent localization patterns compared to primary memory counterparts. Despite these differences, repetitively stimulated brain T[SUB]RM[/SUB] provide similar protection against intracranial infection as primary populations with superior recall-based recruitment of peripheral lymphocytes. As CD8[SUP]+[/SUP] T cells may distinctly seed the brain with each repeated infection of the same host, these findings point to heterogeneity in the brain T[SUB]RM[/SUB] pool that is dictated by prior peripheral antigen stimulation history.
Keywords: CP: Immunology; CP: Neuroscience; brain T(RM); influenza virus; neuroimmunology; repetitive antigen stimulation; viral infection.