High-frequency, functional HIV-specific T-follicular helper and regulatory cells are present within germinal centers in children but not adults
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High-frequency, functional HIV-specific T-follicular helper and regulatory cells are present within germinal centers in children but not adults. / Roider, Julia; Maehara, Takashi; Ngoepe, Abigail; Ramsuran, Duran; Muenchhoff, Maximilian; Adland, Emily; Aicher, Toby; Kazer, Samuel W.; Jooste, Pieter; Karim, Farina; Kuhn, Warren; Shalek, Alex K.; Ndung'u, Thumbi; Morris, Lynn; Moore, Penny L.; Pillai, Shiv; Kløverpris, Henrik; Goulder, Philip; Leslie, Alasdair.
In: Frontiers in Immunology, Vol. 9, 1975, 2018.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - High-frequency, functional HIV-specific T-follicular helper and regulatory cells are present within germinal centers in children but not adults
AU - Roider, Julia
AU - Maehara, Takashi
AU - Ngoepe, Abigail
AU - Ramsuran, Duran
AU - Muenchhoff, Maximilian
AU - Adland, Emily
AU - Aicher, Toby
AU - Kazer, Samuel W.
AU - Jooste, Pieter
AU - Karim, Farina
AU - Kuhn, Warren
AU - Shalek, Alex K.
AU - Ndung'u, Thumbi
AU - Morris, Lynn
AU - Moore, Penny L.
AU - Pillai, Shiv
AU - Kløverpris, Henrik
AU - Goulder, Philip
AU - Leslie, Alasdair
PY - 2018
Y1 - 2018
N2 - Broadly neutralizing antibodies (bnAbs) against HIV-1 are an effective means of preventing transmission. To better understand the mechanisms by which HIV-specific bnAbs naturally develop, we investigated blood and lymphoid tissue in pediatric infection, since potent bnAbs develop with greater frequency in children than adults. As in adults, the frequency of circulating effector T-follicular helper cells (TFH) in HIV infected, treatment naïve children correlates with neutralization breadth. However, major differences between children and adults were also observed both in circulation, and in a small number of tonsil samples. In children, TFH cells are significantly more abundant, both in blood and in lymphoid tissue germinal centers, than in adults. Second, HIV-specific TFH cells are more frequent in pediatric than in adult lymphoid tissue and secrete the signature cytokine IL-21, which HIV-infected adults do not. Third, the enrichment of IL-21-secreting HIV-specific TFH in pediatric lymphoid tissue is accompanied by increased TFH regulation via more abundant regulatory follicular T-cells and HIV-specific CXCR5+ CD8 T-cells compared to adults. The relationship between regulation and neutralization breadth is also observed in the pediatric PBMC samples and correlates with neutralization breadth. Matching neutralization data from lymphoid tissue samples is not available. However, the distinction between infected children and adults in the magnitude, quality and regulation of HIV-specific TFH responses is consistent with the superior ability of children to develop high-frequency, potent bnAbs. These findings suggest the possibility that the optimal timing for next generation vaccine strategies designed to induce high-frequency, potent bnAbs to prevent HIV infection in adults would be in childhood.
AB - Broadly neutralizing antibodies (bnAbs) against HIV-1 are an effective means of preventing transmission. To better understand the mechanisms by which HIV-specific bnAbs naturally develop, we investigated blood and lymphoid tissue in pediatric infection, since potent bnAbs develop with greater frequency in children than adults. As in adults, the frequency of circulating effector T-follicular helper cells (TFH) in HIV infected, treatment naïve children correlates with neutralization breadth. However, major differences between children and adults were also observed both in circulation, and in a small number of tonsil samples. In children, TFH cells are significantly more abundant, both in blood and in lymphoid tissue germinal centers, than in adults. Second, HIV-specific TFH cells are more frequent in pediatric than in adult lymphoid tissue and secrete the signature cytokine IL-21, which HIV-infected adults do not. Third, the enrichment of IL-21-secreting HIV-specific TFH in pediatric lymphoid tissue is accompanied by increased TFH regulation via more abundant regulatory follicular T-cells and HIV-specific CXCR5+ CD8 T-cells compared to adults. The relationship between regulation and neutralization breadth is also observed in the pediatric PBMC samples and correlates with neutralization breadth. Matching neutralization data from lymphoid tissue samples is not available. However, the distinction between infected children and adults in the magnitude, quality and regulation of HIV-specific TFH responses is consistent with the superior ability of children to develop high-frequency, potent bnAbs. These findings suggest the possibility that the optimal timing for next generation vaccine strategies designed to induce high-frequency, potent bnAbs to prevent HIV infection in adults would be in childhood.
KW - Broadly neutralizing antibodies (bnAb)
KW - Follicular CD8 T-cells
KW - Germinal center
KW - Pediatric HIV infection
KW - T-follicular helper cells (Tfh)
KW - T-follicular regulatory helper cells (Tfreg)
KW - Vaccination
U2 - 10.3389/fimmu.2018.01975
DO - 10.3389/fimmu.2018.01975
M3 - Journal article
C2 - 30258437
AN - SCOPUS:85053116226
VL - 9
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 1975
ER -
ID: 208875239