title: On the role of CD4+ T cells in the CD8+ T-cell response elicited by recombinant adenovirus vaccines.
abstract: We have investigated the role of CD4(+) T cells in the development of the CD8(+) T-cell response after immunization with recombinant adenovirus (rAd). In the absence of CD4(+) T cells, the "unhelped" CD8(+) T-cell population exhibited a reduction in primary expansion and long-term survival that appeared to be due to inadequate priming of naïve T cells. There were few functional or phenotypic differences between the helped and unhelped CD8(+) T-cell populations with the exception of O-glycosylated CD43, a marker of effector cells, which was augmented on the unhelped CD8(+) T-cell population. In some cases, the unhelped CD8(+) T-cell population exhibited reduced ability to control virus infection; however, this appeared to be a function of the reduced frequency of antigen-specific CD8(+) T cells. Most notably, the unhelped CD8(+) T-cell population exhibited no defect in secondary expansion. These results provide insight into the role of CD4(+) T cells during the primary CD8(+) T-cell response generated by rAd vaccines and identify potential benefits and issues that must be considered when using adenovirus vaccines under conditions where CD4(+) T-cell function may be limiting, such as vaccination of human immunodeficiency virus patients.
authors: Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
authors: Teng Chih
authors: TC
authors: Yang
authors: James
authors: J
authors: Millar
authors: Timothy
authors: T
authors: Groves
authors: Wenzhong
authors: W
authors: Zhou
authors: Natalie
authors: N
authors: Grinshtein
authors: Robin
authors: R
authors: Parsons
authors: Carole
authors: C
authors: Evelegh
authors: Zhou
authors: Z
authors: Xing
authors: Yonghong
authors: Y
authors: Wan
authors: Jonathan
authors: J
authors: Bramson
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007114:Immunization / Q000379:methods; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D014765:Viral Vaccines