Infection with non-CD4 tropic variant of SIVmac239 accelerates the formation of mature germinal center reactions and elicits antigen specific B cell responses
| Autor: | Yiannis Petros Dimopoulos, Kartika Padhan, Eirini Moysi, Adrienne Swanstrom, Jeffrey D Lifson, Celia LaBranche, Robert Blaire, Pyone Aye, Faith Schiro, Andrew Lackner, Richard Koup, Constantinos Petrovas, Jim Hoxie |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 198:122.9-122.9 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.198.supp.122.9 |
| Popis: | Background What determines the development of germinal centers (GCs) in lymph nodes (LNs) early after HIV/SIV infection is likely to be crucial for developing neutralizing antibodies and B cell memory. Materials and Methods Rhesus macaques were inoculated i.v. with either SIVmac239 (n=2) or iMac239ΔD385 (iMacΔD) (n=4), a CD4-independent variant of SIVmac239 lacking a CD4 binding site (J. Virol. 90:4966, 2016). LNs from different time points were analyzed using polychromatic flow cytometry and multiplexed confocal imaging. Results In contrast to SIVmac239, iMacΔD infection was associated with relative preservation of total and CD28hiCD95hi memory CD4 T cells, consistent with its compromised capacity to target CD4 T cells. Imaging analysis revealed accelerated formation of mature, polarized GCs in iMacΔD compared to SIVmac239 infected animals, a profile associated with i) increased frequencies of PD-1hiBcl-6hi CD4 T cells, ii) higher levels of IL-10 and IL-21 within the follicles, iii) increased frequency of PH2AX+ (a required factor for isotype switching) B cells, iv) lower levels of Fas-L in the follicular areas, associated with lower TUNEL (cell death) positivity and v) lower accumulation of CD163+ cells (monocytes/macrophages; a surrogate of local inflammation) in proximity to follicles. The observed GC dynamics associate with earlier virus-specific antibody responses in iMacΔD compared to SIVmac239. Conclusions Our data indicate that CD4 tropism of SIV greatly affects the development of GC reactions early after infection. The iMacΔD model could provide critical information on how GC reactions can be manipulated to augment the generation of neutralizing antibodies and B cell memory. |
| Databáze: | OpenAIRE |
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