title: CD4 T follicular helper cell dynamics during SIV infection.
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.
authors.affiliation: Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA. petrovasc@mail.nih.gov
authors.forename: Constantinos
authors.initials: C
authors.lastname: Petrovas
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Gerner
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Boswell
authors.forename: Kaska
authors.initials: K
authors.lastname: Wloka
authors.forename: Emily C
authors.initials: EC
authors.lastname: Smith
authors.forename: David R
authors.initials: DR
authors.lastname: Ambrozak
authors.forename: Netanya G
authors.initials: NG
authors.lastname: Sandler
authors.forename: Katherina J
authors.initials: KJ
authors.lastname: Timmer
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Pan
authors.forename: Amanda
authors.initials: A
authors.lastname: Poholek
authors.forename: Srinivas S
authors.initials: SS
authors.lastname: Rao
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Germain
authors.forename: Elias K
authors.initials: EK
authors.lastname: Haddad
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016923:Cell Death; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression; D018858:Germinal Center / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta; D020411:Oligonucleotide Array Sequence Analysis; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D000914:Antibodies, Viral; D015704:CD4 Antigens; D016207:Cytokines; D051257:Proto-Oncogene Proteins c-maf; D049349:Receptors, Lysosphingolipid; D020825:T-Box Domain Proteins; D014157:Transcription Factors