Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals, Infection and Immunization
2.2. Sample Collection and Processing
2.3. Quantification of Plasma Cytokines, Immunoglobulins and Antigen-Specific Antibodies
2.4. Flow Cytometry Analyses
2.5. Immunohistochemistry and Digital Image Analysis
2.6. Statistical Analysis
3. Results
3.1. Humoral Response upon SIV-Infection or TT-Vaccination
3.2. Systemic Inflammation upon SIV-Infection or TT-Vaccination
3.3. Differences in Nodular B-Cells and TFH Associated with Responses to TT or SIV
3.4. Differences in Splenic B-Cells Associated with Responses to TT or SIV
3.5. Major Differences in Splenic TFH and Other mCD4 T-Cell Subsets between the Two Groups
3.6. BAFF-R and TACI Expression on GC B-Cells and TFH
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Moir, S.; Fauci, A.S. B-cell responses to HIV infection. Immunol. Rev. 2017, 275, 33–48. [Google Scholar] [CrossRef]
- Chiodi, F.; Scarlatti, G. Editorial: HIV-induced damage of B cells and production of HIV neutralizing antibodies. Front. Immunol. 2018, 9, 297. [Google Scholar] [CrossRef]
- Bannard, O.; Cyster, J.G. Germinal centers: Programmed for affinity maturation and antibody diversification. Curr. Opin. Immunol. 2017, 45, 21–30. [Google Scholar] [CrossRef] [PubMed]
- Binder, S.C.; Meyer-Hermann, M. Implications of intravital imaging of murine germinal centers on the control of B cell selection and division. Front. Immunol. 2016, 7, 593. [Google Scholar] [CrossRef] [PubMed]
- Victora, G.D.; Nussenzweig, M.C. Germinal centers. Annu. Rev. Immunol. 2012, 30, 429–457. [Google Scholar] [CrossRef] [PubMed]
- Sanchez-Merino, V.; Fabra-Garcia, A.; Gonzalez, N.; Nicolas, D.; Merino-Mansilla, A.; Manzardo, C.; Ambrosioni, J.; Schultz, A.; Meyerhans, A.; Mascola, J.R.; et al. Detection of broadly neutralizing activity within the first months of HIV-1 infection. J. Virol. 2016, 90, 5231–5245. [Google Scholar] [CrossRef] [PubMed]
- Borrow, P.; Moody, M.A. Immunologic characteristics of HIV-infected individuals who make broadly neutralizing antibodies. Immunol. Rev. 2017, 275, 62–78. [Google Scholar] [CrossRef]
- Verkoczy, L.; Diaz, M. Autoreactivity in HIV-1 broadly neutralizing antibodies: Implications for their function and induction by vaccination. Curr. Opin. HIV AIDS 2014, 9, 224–234. [Google Scholar] [CrossRef] [PubMed]
- Liao, H.X.; Chen, X.; Munshaw, S.; Zhang, R.; Marshall, D.J.; Vandergrift, N.; Whitesides, J.F.; Lu, X.; Yu, J.S.; Hwang, K.K.; et al. Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated. J. Exp. Med. 2011, 208, 2237–2249. [Google Scholar] [CrossRef] [PubMed]
- Burton, D.R.; Mascola, J.R. Antibody responses to envelope glycoproteins in HIV-1 infection. Nat. Immunol. 2015, 16, 571–576. [Google Scholar] [CrossRef]
- Schroeder, K.M.S.; Agazio, A.; Strauch, P.J.; Jones, S.T.; Thompson, S.B.; Harper, M.S.; Pelanda, R.; Santiago, M.L.; Torres, R.M. Breaching peripheral tolerance promotes the production of HIV-1-neutralizing antibodies. J. Exp. Med. 2017, 214, 2283–2302. [Google Scholar] [CrossRef]
- Lee, J.H.; Ozorowski, G.; Ward, A.B. Cryo-em structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer. Science 2016, 351, 1043–1048. [Google Scholar] [CrossRef]
- Havenar-Daughton, C.; Carnathan, D.G.; Torrents de la Pena, A.; Pauthner, M.; Briney, B.; Reiss, S.M.; Wood, J.S.; Kaushik, K.; van Gils, M.J.; Rosales, S.L.; et al. Direct probing of germinal center responses reveals immunological features and bottlenecks for neutralizing antibody responses to HIV env trimer. Cell Rep. 2016, 17, 2195–2209. [Google Scholar] [CrossRef]
- Pauthner, M.; Havenar-Daughton, C.; Sok, D.; Nkolola, J.P.; Bastidas, R.; Boopathy, A.V.; Carnathan, D.G.; Chandrashekar, A.; Cirelli, K.M.; Cottrell, C.A.; et al. Elicitation of robust tier 2 neutralizing antibody responses in nonhuman primates by HIV envelope trimer immunization using optimized approaches. Immunity 2017, 46, 1073–1088.e1076. [Google Scholar] [CrossRef] [PubMed]
- Pauthner, M.G.; Nkolola, J.P.; Havenar-Daughton, C.; Murrell, B.; Reiss, S.M.; Bastidas, R.; Prevost, J.; Nedellec, R.; von Bredow, B.; Abbink, P.; et al. Vaccine-induced protection from homologous tier 2 SHIV challenge in nonhuman primates depends on serum-neutralizing antibody titers. Immunity 2019, 50, 241–252.e6. [Google Scholar] [CrossRef] [PubMed]
- Muir, R.; Metcalf, T.; Tardif, V.; Takata, H.; Phanuphak, N.; Kroon, E.; Colby, D.J.; Trichavaroj, R.; Valcour, V.; Robb, M.L.; et al. Altered memory circulating T follicular helper-B cell interaction in early acute hiv infection. PLoS Pathog. 2016, 12, e1005777. [Google Scholar] [CrossRef] [PubMed]
- Borhis, G.; Trovato, M.; Ibrahim, H.M.; Isnard, S.; Le Grand, R.; Bosquet, N.; Richard, Y. Impact of BAFF blockade on inflammation, germinal center reaction and effector B-cells during acute siv infection. Front. Immunol. 2020, 11, 252. [Google Scholar] [CrossRef]
- Perreau, M.; Savoye, A.L.; De Crignis, E.; Corpataux, J.M.; Cubas, R.; Haddad, E.K.; De Leval, L.; Graziosi, C.; Pantaleo, G. Follicular helper t cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J. Exp. Med. 2013, 210, 143–156. [Google Scholar] [CrossRef]
- Fukazawa, Y.; Lum, R.; Okoye, A.A.; Park, H.; Matsuda, K.; Bae, J.Y.; Hagen, S.I.; Shoemaker, R.; Deleage, C.; Lucero, C.; et al. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat. Med. 2015, 21, 132–139. [Google Scholar] [CrossRef]
- Linterman, M.A.; Pierson, W.; Lee, S.K.; Kallies, A.; Kawamoto, S.; Rayner, T.F.; Srivastava, M.; Divekar, D.P.; Beaton, L.; Hogan, J.J.; et al. Foxp3+ follicular regulatory T cells control the germinal center response. Nat. Med. 2011, 17, 975–982. [Google Scholar] [CrossRef] [PubMed]
- Fan, W.; Demers, A.J.; Wan, Y.; Li, Q. Altered ratio of T follicular helper cells to T follicular regulatory cells correlates with autoreactive antibody response in simian immunodeficiency virus-infected rhesus macaques. J. Immunol. 2018, 200, 3180–3187. [Google Scholar] [CrossRef]
- Laidlaw, B.J.; Lu, Y.; Amezquita, R.A.; Weinstein, J.S.; Vander Heiden, J.A.; Gupta, N.T.; Kleinstein, S.H.; Kaech, S.M.; Craft, J. Interleukin-10 from CD4(+) follicular regulatory T cells promotes the germinal center response. Sci. Immunol. 2017, 2, eaan4767. [Google Scholar] [CrossRef]
- Xie, M.M.; Dent, A.L. Unexpected help: Follicular regulatory T cells in the germinal center. Front. Immunol. 2018, 9, 1536. [Google Scholar] [CrossRef]
- Miller, S.M.; Miles, B.; Guo, K.; Folkvord, J.; Meditz, A.L.; McCarter, M.D.; Levy, D.N.; MaWhinney, S.; Santiago, M.L.; Connick, E. Follicular regulatory T cells are highly permissive to R5-tropic HIV-1. J. Virol. 2017, 91, e00430-17. [Google Scholar] [CrossRef]
- Bronnimann, M.P.; Skinner, P.J.; Connick, E. The B-cell follicle in HIV infection: Barrier to a cure. Front. Immunol. 2018, 9, 20. [Google Scholar] [CrossRef] [PubMed]
- Karnell, J.L.; Kumar, V.; Wang, J.; Wang, S.; Voynova, E.; Ettinger, R. Role of CD11c(+) T-bet(+) B cells in human health and disease. Cell Immunol. 2017, 321, 40–45. [Google Scholar] [CrossRef] [PubMed]
- Obeng-Adjei, N.; Portugal, S.; Holla, P.; Li, S.; Sohn, H.; Ambegaonkar, A.; Skinner, J.; Bowyer, G.; Doumbo, O.K.; Traore, B.; et al. Malaria-induced interferon-gamma drives the expansion of Tbethi atypical memory B cells. PLoS Pathog. 2017, 13, e1006576. [Google Scholar] [CrossRef] [PubMed]
- Jenks, S.A.; Cashman, K.S.; Zumaquero, E.; Marigorta, U.M.; Patel, A.V.; Wang, X.; Tomar, D.; Woodruff, M.C.; Simon, Z.; Bugrovsky, R.; et al. Distinct effector B cells induced by unregulated toll-like receptor 7 contribute to pathogenic responses in systemic lupus erythematosus. Immunity 2018, 49, 725–739 e726. [Google Scholar] [CrossRef]
- Knox, J.J.; Buggert, M.; Kardava, L.; Seaton, K.E.; Eller, M.A.; Canaday, D.H.; Robb, M.L.; Ostrowski, M.A.; Deeks, S.G.; Slifka, M.K.; et al. T-bet+ B cells are induced by human viral infections and dominate the hiv gp140 response. JCI Insight 2017, 2, 92943. [Google Scholar] [CrossRef] [PubMed]
- Rubtsova, K.; Rubtsov, A.V.; van Dyk, L.F.; Kappler, J.W.; Marrack, P. T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance. Proc. Natl. Acad. Sci. USA 2013, 110, E3216–E3224. [Google Scholar] [CrossRef]
- Siewe, B.; Nipper, A.J.; Sohn, H.; Stapleton, J.T.; Landay, A. FcRL4 expression identifies a pro-inflammatory B cell subset in viremic hiv-infected subjects. Front. Immunol. 2017, 8, 1339. [Google Scholar] [CrossRef]
- Portugal, S.; Tipton, C.M.; Sohn, H.; Kone, Y.; Wang, J.; Li, S.; Skinner, J.; Virtaneva, K.; Sturdevant, D.E.; Porcella, S.F.; et al. Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function. Elife 2015, 4, e07218. [Google Scholar] [CrossRef]
- Moir, S.; Fauci, A.S. Insights into B cells and HIV-specific B-cell responses in HIV-infected individuals. Immunol. Rev. 2013, 254, 207–224. [Google Scholar] [CrossRef] [PubMed]
- Borhis, G.; Richard, Y. Subversion of the B-cell compartment during parasitic, bacterial, and viral infections. BMC Immunol. 2015, 16, 15. [Google Scholar] [CrossRef] [PubMed]
- Perez-Mazliah, D.; Gardner, P.J.; Schweighoffer, E.; McLaughlin, S.; Hosking, C.; Tumwine, I.; Davis, R.S.; Potocnik, A.J.; Tybulewicz, V.L.; Langhorne, J. Plasmodium-specific atypical memory B cells are short-lived activated B cells. Elife 2018, 7, e39800. [Google Scholar] [CrossRef] [PubMed]
- Kardava, L.; Moir, S.; Shah, N.; Wang, W.; Wilson, R.; Buckner, C.M.; Santich, B.H.; Kim, L.J.; Spurlin, E.E.; Nelson, A.K.; et al. Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals. J. Clin. Investig. 2014, 124, 3252–3262. [Google Scholar] [CrossRef]
- Titanji, K.; Velu, V.; Chennareddi, L.; Vijay-Kumar, M.; Gewirtz, A.T.; Freeman, G.J.; Amara, R.R. Acute depletion of activated memory B cells involves the PD-1 pathway in rapidly progressing SIV-infected macaques. J. Clin. Investig. 2010, 120, 3878–3890. [Google Scholar] [CrossRef]
- Lau, D.; Lan, L.Y.; Andrews, S.F.; Henry, C.; Rojas, K.T.; Neu, K.E.; Huang, M.; Huang, Y.; DeKosky, B.; Palm, A.E.; et al. Low CD21 expression defines a population of recent germinal center graduates primed for plasma cell differentiation. Sci. Immunol. 2017, 2, eaai8153. [Google Scholar] [CrossRef]
- Austin, J.W.; Buckner, C.M.; Kardava, L.; Wang, W.; Zhang, X.; Melson, V.A.; Swanson, R.G.; Martins, A.J.; Zhou, J.Q.; Hoehn, K.B.; et al. Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation. Sci. Transl. Med. 2019, 11, eaax0904. [Google Scholar] [CrossRef]
- Giesecke, C.; Frolich, D.; Reiter, K.; Mei, H.E.; Wirries, I.; Kuhly, R.; Killig, M.; Glatzer, T.; Stolzel, K.; Perka, C.; et al. Tissue distribution and dependence of responsiveness of human antigen-specific memory B cells. J. Immunol. 2014, 192, 3091–3100. [Google Scholar] [CrossRef]
- Livingston, K.A.; Jiang, X.; Stephensen, C.B. CD4 T-helper cell cytokine phenotypes and antibody response following tetanus toxoid booster immunization. J. Immunol. Methods 2013, 390, 18–29. [Google Scholar] [CrossRef]
- Pallikkuth, S.; De Armas, L.R.; Pahwa, R.; Rinaldi, S.; George, V.K.; Sanchez, C.M.; Pan, L.; Dickinson, G.; Rodriguez, A.; Fischl, M.; et al. Impact of aging and hiv infection on serologic response to seasonal influenza vaccination. AIDS 2018, 32, 1085–1094. [Google Scholar] [CrossRef]
- Parmigiani, A.; Alcaide, M.L.; Freguja, R.; Pallikkuth, S.; Frasca, D.; Fischl, M.A.; Pahwa, S. Impaired antibody response to influenza vaccine in hiv-infected and uninfected aging women is associated with immune activation and inflammation. PLoS ONE 2013, 8, e79816. [Google Scholar] [CrossRef]
- Le Grand, R.; Clayette, P.; Noack, O.; Vaslin, B.; Theodoro, F.; Michel, G.; Roques, P.; Dormont, D. An animal model for antilentiviral therapy: Effect of zidovudine on viral load during acute infection after exposure of macaques to simian immunodeficiency virus. AIDS Res. Hum. Retrovir. 1994, 10, 1279–1287. [Google Scholar] [CrossRef] [PubMed]
- Peruchon, S.; Chaoul, N.; Burelout, C.; Delache, B.; Brochard, P.; Laurent, P.; Cognasse, F.; Prevot, S.; Garraud, O.; Le Grand, R.; et al. Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection. PLoS ONE 2009, 4, e5966. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Chaoul, N.; Burelout, C.; Peruchon, S.; van Buu, B.N.; Laurent, P.; Proust, A.; Raphael, M.; Garraud, O.; Le Grand, R.; Prevot, S.; et al. Default in plasma and intestinal IgA responses during acute infection by simian immunodeficiency virus. Retrovirology 2012, 9, 43. [Google Scholar] [CrossRef] [PubMed]
- Li, G.; Cheng, M.; Nunoya, J.; Cheng, L.; Guo, H.; Yu, H.; Liu, Y.J.; Su, L.; Zhang, L. Plasmacytoid dendritic cells suppress HIV-1 replication but contribute to HIV-1 induced immunopathogenesis in humanized mice. PLoS Pathog. 2014, 10, e1004291. [Google Scholar] [CrossRef]
- Hogenesch, H. Mechanism of immunopotentiation and safety of aluminum adjuvants. Front. Immunol. 2012, 3, 406. [Google Scholar] [CrossRef] [PubMed]
- Lu, F.; Hogenesch, H. Kinetics of the inflammatory response following intramuscular injection of aluminum adjuvant. Vaccine 2013, 31, 3979–3986. [Google Scholar] [CrossRef]
- Cohen, K.W.; Dugast, A.S.; Alter, G.; McElrath, M.J.; Stamatatos, L. HIV-1 single-stranded rna induces CXCL13 secretion in human monocytes via TLR7 activation and plasmacytoid dendritic cell-derived type I IFN. J. Immunol. 2015, 194, 2769–2775. [Google Scholar] [CrossRef]
- Stacey, A.R.; Norris, P.J.; Qin, L.; Haygreen, E.A.; Taylor, E.; Heitman, J.; Lebedeva, M.; DeCamp, A.; Li, D.; Grove, D.; et al. Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J. Virol. 2009, 83, 3719–3733. [Google Scholar] [CrossRef]
- Liovat, A.S.; Rey-Cuille, M.A.; Lecuroux, C.; Jacquelin, B.; Girault, I.; Petitjean, G.; Zitoun, Y.; Venet, A.; Barre-Sinoussi, F.; Lebon, P.; et al. Acute plasma biomarkers of T cell activation set-point levels and of disease progression in HIV-1 infection. PLoS ONE 2012, 7, e46143. [Google Scholar] [CrossRef] [PubMed]
- Havenar-Daughton, C.; Lindqvist, M.; Heit, A.; Wu, J.E.; Reiss, S.M.; Kendric, K.; Belanger, S.; Kasturi, S.P.; Landais, E.; Akondy, R.S.; et al. CXCL13 is a plasma biomarker of germinal center activity. Proc. Natl. Acad. Sci. USA 2016, 113, 2702–2707. [Google Scholar] [CrossRef] [PubMed]
- Mabuka, J.M.; Dugast, A.S.; Muema, D.M.; Reddy, T.; RamLakhan, Y.; Euler, Z.; Ismail, N.; Moodley, A.; Dong, K.L.; Morris, L.; et al. Plasma CXCL13 but not B cell frequencies in acute HIV infection predicts emergence of cross-neutralizing antibodies. Front. Immunol. 2017, 8, 1104. [Google Scholar] [CrossRef]
- Roider, J.; Porterfield, J.Z.; Ogongo, P.; Muenchhoff, M.; Adland, E.; Groll, A.; Morris, L.; Moore, P.L.; Ndung’u, T.; Kloverpris, H.; et al. Plasma IL-5 but not CXCL13 correlates with neutralization breadth in HIV-infected children. Front. Immunol. 2019, 10, 1497. [Google Scholar] [CrossRef] [PubMed]
- Mehraj, V.; Ramendra, R.; Isnard, S.; Dupuy, F.P.; Lebouche, B.; Costiniuk, C.; Thomas, R.; Szabo, J.; Baril, J.G.; Trottier, B.; et al. CXCL13 as a biomarker of immune activation during early and chronic HIV infection. Front. Immunol. 2019, 10, 289. [Google Scholar] [CrossRef]
- Richardson, S.I.; Chung, A.W.; Natarajan, H.; Mabvakure, B.; Mkhize, N.N.; Garrett, N.; Abdool Karim, S.; Moore, P.L.; Ackerman, M.E.; Alter, G.; et al. HIV-specific Fc effector function early in infection predicts the development of broadly neutralizing antibodies. PLoS Pathog. 2018, 14, e1006987. [Google Scholar] [CrossRef]
- Ferrando-Martinez, S.; Moysi, E.; Pegu, A.; Andrews, S.; Nganou Makamdop, K.; Ambrozak, D.; McDermott, A.B.; Palesch, D.; Paiardini, M.; Pavlakis, G.N.; et al. Accumulation of follicular CD8+ T cells in pathogenic siv infection. J. Clin. Investig. 2018, 128, 2089–2103. [Google Scholar] [CrossRef]
- Miles, B.; Miller, S.M.; Connick, E. CD4 T follicular helper and regulatory cell dynamics and function in HIV infection. Front. Immunol. 2016, 7, 659. [Google Scholar] [CrossRef]
- Sayin, I.; Radtke, A.J.; Vella, L.A.; Jin, W.; Wherry, E.J.; Buggert, M.; Betts, M.R.; Herati, R.S.; Germain, R.N.; Canaday, D.H. Spatial distribution and function of T follicular regulatory cells in human lymph nodes. J. Exp. Med. 2018, 215, 1531–1542. [Google Scholar] [CrossRef]
- Frolich, D.; Giesecke, C.; Mei, H.E.; Reiter, K.; Daridon, C.; Lipsky, P.E.; Dorner, T. Secondary immunization generates clonally related antigen-specific plasma cells and memory B cells. J. Immunol. 2010, 185, 3103–3110. [Google Scholar] [CrossRef] [PubMed]
- Paus, D.; Phan, T.G.; Chan, T.D.; Gardam, S.; Basten, A.; Brink, R. Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation. J. Exp. Med. 2006, 203, 1081–1091. [Google Scholar] [CrossRef] [PubMed]
- Moir, S.; Malaspina, A.; Pickeral, O.K.; Donoghue, E.T.; Vasquez, J.; Miller, N.J.; Krishnan, S.R.; Planta, M.A.; Turney, J.F.; Justement, J.S.; et al. Decreased survival of B cells of HIV-viremic patients mediated by altered expression of receptors of the TNF superfamily. J. Exp. Med. 2004, 200, 587–599. [Google Scholar] [CrossRef]
- Schweighoffer, E.; Vanes, L.; Nys, J.; Cantrell, D.; McCleary, S.; Smithers, N.; Tybulewicz, V.L. The BAFF receptor transduces survival signals by co-opting the B cell receptor signaling pathway. Immunity 2013, 38, 475–488. [Google Scholar] [CrossRef] [PubMed]
- Coquery, C.M.; Loo, W.M.; Wade, N.S.; Bederman, A.G.; Tung, K.S.; Lewis, J.E.; Hess, H.; Erickson, L.D. BAFF regulates follicular helper T cells and affects their accumulation and interferon-gamma production in autoimmunity. Arthritis Rheumatol. 2015, 67, 773–784. [Google Scholar] [CrossRef]
Lymph Node | Spleen | ||||
---|---|---|---|---|---|
Spearman Rank Test a | Spearman Rank Test a | ||||
Cytokine b | Cell Subset c | p Values | rho | p Values | rho |
CD14hi monocytes | * | 0.5801 | ns | ||
CD16+ monocytes | ** | 0.640 | ns | ||
CXCL13 | Total DC d | ns | ns | ||
cDC2 | ns | 0.064 | 0.492 | ||
pDC | ns | ns | |||
CD14hi monocytes | * | 0.611 | ns | ||
CD16+ monocytes | * | 0.571 | ns | ||
IFNα | Total DC | * | 0.567 | ns | |
cDC2 | ns | ns | |||
pDC | ns | ns | |||
CD14hi monocytes | ** | 0.737 | * | 0.555 | |
CD16+ monocytes | *** | 0.767 | ns | ||
CXCL10 | Total DC | * | 0.603 | * | 0.632 |
cDC2 | ns | ns | |||
pDC | * | 0.616 | ns | ||
CD14hi monocytes | ** | 0.748 | 0.056 | 0.491 | |
CD16+ monocytes | *** | 0.811 | ns | ||
BAFF | Total DC | * | 0.539 | * | 0.569 |
cDC2 | ns | ** | |||
pDC | ** | 0.677 | ns | 0.690 |
Subset | Cytokine a | Spearman Rank Test b | |
---|---|---|---|
p Values | Rho | ||
IFNα | ** | 0.761 | |
TFH | CXCL10 | ** | 0.743 |
% in mCD4 T-cells | CXCL13 | * | 0.571 |
IFNα | **** | 0.841 | |
CD68+ cells | CXCL10 | **** | 0.853 |
no. per GC | CXCL13 | ns | |
BAFF | ** | 0.734 | |
IFNα | **** | 0.854 | |
fCD8 T-cells | CXCL10 | ** | 0.730 |
no. per GC | CXCL13 | * | 0.584 |
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Trovato, M.; Ibrahim, H.M.; Isnard, S.; Le Grand, R.; Bosquet, N.; Borhis, G.; Richard, Y. Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen. Viruses 2021, 13, 263. https://doi.org/10.3390/v13020263
Trovato M, Ibrahim HM, Isnard S, Le Grand R, Bosquet N, Borhis G, Richard Y. Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen. Viruses. 2021; 13(2):263. https://doi.org/10.3390/v13020263
Chicago/Turabian StyleTrovato, Maria, Hany M. Ibrahim, Stephane Isnard, Roger Le Grand, Nathalie Bosquet, Gwenoline Borhis, and Yolande Richard. 2021. "Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen" Viruses 13, no. 2: 263. https://doi.org/10.3390/v13020263
APA StyleTrovato, M., Ibrahim, H. M., Isnard, S., Le Grand, R., Bosquet, N., Borhis, G., & Richard, Y. (2021). Distinct Features of Germinal Center Reactions in Macaques Infected by SIV or Vaccinated with a T-Dependent Model Antigen. Viruses, 13(2), 263. https://doi.org/10.3390/v13020263