Circulating CXCR5(+)CXCR3(+)PD-1(lo) Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth
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Circulating CXCR5(+)CXCR3(+)PD-1(lo) Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth. / Martin-Gayo, Enrique; Cronin, Jacqueline; Hickman, Taylor; Ouyang, Zhengyu; Lindqvist, Madelene; Kolb, Kellie E; Schulze Zur Wiesch, Julian; Cubas, Rafael; Porichis, Filippos; Shalek, Alex K; Lunzen, Jan Van; Haddad, Elias K; Walker, Bruce D; Kaufmann, Daniel E; Lichterfeld, Mathias; Yu, Xu G.
in: JCI INSIGHT, Jahrgang 2, Nr. 2, 26.01.2017, S. e89574.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Circulating CXCR5(+)CXCR3(+)PD-1(lo) Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth
AU - Martin-Gayo, Enrique
AU - Cronin, Jacqueline
AU - Hickman, Taylor
AU - Ouyang, Zhengyu
AU - Lindqvist, Madelene
AU - Kolb, Kellie E
AU - Schulze Zur Wiesch, Julian
AU - Cubas, Rafael
AU - Porichis, Filippos
AU - Shalek, Alex K
AU - Lunzen, Jan Van
AU - Haddad, Elias K
AU - Walker, Bruce D
AU - Kaufmann, Daniel E
AU - Lichterfeld, Mathias
AU - Yu, Xu G
PY - 2017/1/26
Y1 - 2017/1/26
N2 - HIV-1-specific broadly neutralizing antibodies (bnAbs) typically develop in individuals with continuous high-level viral replication and increased immune activation, conditions that cannot be reproduced during prophylactic immunization. Understanding mechanisms supporting bnAb development in the absence of high-level viremia may be important for designing bnAb-inducing immunogens. Here, we show that the breadth of neutralizing antibody responses in HIV-1 controllers was associated with a relative enrichment of circulating CXCR5(+)CXCR3(+)PD-1(lo) CD4(+) T cells. These CXCR3(+)PD-1(lo) Tfh-like cells were preferentially induced in vitro by functionally superior dendritic cells from controller neutralizers, and able to secrete IL-21 and support B cells. In addition, these CXCR3(+)PD-1(lo) Tfh-like cells contained higher proportions of stem cell-like memory T cells, and upon antigenic stimulation differentiated into PD-1(hi) Tfh-like cells in a Notch-dependent manner. Together, these data suggest that CXCR5(+)CXCR3(+)PD-1(lo) cells represent a dendritic cell-primed precursor cell population for PD-1(hi) Tfh-like cells that may contribute to the generation of bnAbs in the absence of high-level viremia.
AB - HIV-1-specific broadly neutralizing antibodies (bnAbs) typically develop in individuals with continuous high-level viral replication and increased immune activation, conditions that cannot be reproduced during prophylactic immunization. Understanding mechanisms supporting bnAb development in the absence of high-level viremia may be important for designing bnAb-inducing immunogens. Here, we show that the breadth of neutralizing antibody responses in HIV-1 controllers was associated with a relative enrichment of circulating CXCR5(+)CXCR3(+)PD-1(lo) CD4(+) T cells. These CXCR3(+)PD-1(lo) Tfh-like cells were preferentially induced in vitro by functionally superior dendritic cells from controller neutralizers, and able to secrete IL-21 and support B cells. In addition, these CXCR3(+)PD-1(lo) Tfh-like cells contained higher proportions of stem cell-like memory T cells, and upon antigenic stimulation differentiated into PD-1(hi) Tfh-like cells in a Notch-dependent manner. Together, these data suggest that CXCR5(+)CXCR3(+)PD-1(lo) cells represent a dendritic cell-primed precursor cell population for PD-1(hi) Tfh-like cells that may contribute to the generation of bnAbs in the absence of high-level viremia.
KW - Journal Article
U2 - 10.1172/jci.insight.89574
DO - 10.1172/jci.insight.89574
M3 - SCORING: Journal article
C2 - 28138558
VL - 2
SP - e89574
JO - JCI INSIGHT
JF - JCI INSIGHT
SN - 2379-3708
IS - 2
ER -
