title: Defining T-cell-mediated immune responses in rotavirus-infected juvenile rhesus macaques.
abstract: The appearance of virus-specific CD4(+) and/or CD8(+) T lymphocytes in peripheral blood of captive juvenile rhesus macaques (Macaca mulatta) was observed following rotavirus infection. These cell-mediated immune responses were measured following experimental or natural infection after rotavirus was isolated from stool specimens of asymptomatic animals. The virus isolated was a new strain of simian rotavirus that we named TUCH (for Tulane University and Cincinnati Children's Hospital). Restimulation of peripheral T lymphocytes by inactivated double- or triple-layered TUCH rotavirus particles containing either VP6 or VP4 and VP7 on their respective surfaces resulted in increased quantities of interleukin-6 (IL-6) and IL-12 in cell culture supernatants. Recall responses to rotavirus by CD4(+) and CD8(+) T lymphocytes were associated with accumulation of intracellular IL-6 and gamma interferon. Antigen presentation of TUCH rotavirus to lymphocytes was mediated via differentiated cultures of monocyte-derived dendritic (HLA-DR(+)) cells. This is the first report demonstrating cell-mediated immune responses to rotavirus in nonhuman primates. Further exploration of rhesus macaques in vaccine trials with human rotavirus vaccine candidates is the major objective of future studies.
authors.affiliation: Division of Microbiology and Immunology, Tulane National Primate Research Center, 18703 Three Rivers Rd., Covington, LA 70433, USA. ksestak@tulane.edu
authors.forename: K
authors.initials: K
authors.lastname: Sestak
authors.forename: M M
authors.initials: MM
authors.lastname: McNeal
authors.forename: A
authors.initials: A
authors.lastname: Choi
authors.forename: M J
authors.initials: MJ
authors.lastname: Cole
authors.forename: G
authors.initials: G
authors.lastname: Ramesh
authors.forename: X
authors.initials: X
authors.lastname: Alvarez
authors.forename: P P
authors.initials: PP
authors.lastname: Aye
authors.forename: R P
authors.initials: RP
authors.lastname: Bohm
authors.forename: M
authors.initials: M
authors.lastname: Mohamadzadeh
authors.forename: R L
authors.initials: RL
authors.lastname: Ward
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005243:Feces / Q000821:virology; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D012401:Rotavirus / Q000145:classification / Q000276:immunology* / Q000302:isolation & purification; D012400:Rotavirus Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D015850:Interleukin-6; C060339:VP4 protein, Rotavirus; C061332:VP6 protein, Rotavirus; C050779:VP7 protein, Rotavirus; D018664:Interleukin-12; D007371:Interferon-gamma