CD4 T follicular helper cell dynamics during SIV infection

Constantinos Petrovas, Takuya Yamamoto, Michael Y. Gerner, Kristin L. Boswell, Kaska Wloka, Emily C. Smith, David R. Ambrozak, Netanya G. Sandler, Katherina J. Timmer, Xiaoyong Sun, Li Pan, Amanda Poholek, Srinivas S. Rao, Jason M. Brenchley, S. Munir Alam, Georgia D. Tomaras, Mario Roederer, Daniel C. Douek, Robert A. Seder, Ronald N. GermainElias K. Haddad, Richard A. Koup

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232 Scopus citations

Abstract

CD4 T follicular helper (TFH) cells interact with and stimulate the generation of antigen-specific B cells. TFH cell interaction with B cells correlates with production of SIV-specific immunoglobulins. However, the fate of TFH cells and their participation in SIV-induced antibody production is not well understood. We investigated the phenotype, function, location, and molecular signature of TFH cells in rhesus macaques. Similar to their human counterparts, TFH cells in rhesus macaques represented a heterogeneous population with respect to cytokine function. In a highly differentiated subpopulation of TFH cells, characterized by CD150lo expression, production of Th1 cytokines was compromised while IL-4 production was augmented, and cells exhibited decreased survival, cycling, and trafficking capacity. TFH cells exhibited a distinct gene profile that was markedly altered by SIV infection. TFH cells were infected by SIV; yet, in some animals, these cells actually accumulated during chronic SIV infection. Generalized immune activation and increased IL-6 production helped drive TFH differentiation during SIV infection. Accumulation of TFH cells was associated with increased frequency of activated germinal center B cells and SIV-specific antibodies. Therefore, chronic SIV does not disturb the ability of TFH cells to help B cell maturation and production of SIV-specific immunoglobulins.

Original languageEnglish (US)
Pages (from-to)3281-3294
Number of pages14
JournalJournal of Clinical Investigation
Volume122
Issue number9
DOIs
StatePublished - Sep 4 2012

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ASJC Scopus subject areas

  • Medicine(all)

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Petrovas, C., Yamamoto, T., Gerner, M. Y., Boswell, K. L., Wloka, K., Smith, E. C., Ambrozak, D. R., Sandler, N. G., Timmer, K. J., Sun, X., Pan, L., Poholek, A., Rao, S. S., Brenchley, J. M., Alam, S. M., Tomaras, G. D., Roederer, M., Douek, D. C., Seder, R. A., ... Koup, R. A. (2012). CD4 T follicular helper cell dynamics during SIV infection. Journal of Clinical Investigation, 122(9), 3281-3294. https://doi.org/10.1172/JCI63039