| Autor: |
Martin-Gayo, Enrique, Cronin, Jacqueline, Hickman, Taylor, Ouyang, Zhengyu, Lindqvist, Madelene, Schulze zur Wiesch, Julian, Cubas, Rafael, Porichis, Filippos, van Lunzen, Jan, Haddad, Elias K., Walker, Bruce D., Kaufmann, Daniel E., Lichterfeld, Mathias, Yu, Xu G., Kolb, Kellie Elizabeth, Shalek, Alexander K |
| Přispěvatelé: |
Institute for Medical Engineering and Science, Shalek, Alex K., Kolb, Kellie Elizabeth, Shalek, Alexander K |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Zdroj: |
Prof. Shalek via Erja Kajosalo |
| Popis: |
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[superscript +]CXCR3[superscript +]PD-1[superscript lo] CD4[superscript +] T cells. These CXCR3[superscript +]PD-1[superscript 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[superscript +]PD-1[superscript lo] Tfh-like cells contained higher proportions of stem cell–like memory T cells, and upon antigenic stimulation differentiated into PD-1[superscript hi ]Tfh-like cells in a Notch-dependent manner. Together, these data suggest that CXCR5[superscript +]CXCR3[superscript +]PD-1[superscript lo] cells represent a dendritic cell–primed precursor cell population for PD-1hi Tfh-like cells that may contribute to the generation of bnAbs in the absence of high-level viremia. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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