On the role of CD4+ T cells in the CD8+ T-cell response elicited by recombinant adenovirus vaccines.
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.
Yang
Teng Chih
TC
Department of Pathology and Molecular Medicine, Center for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
Millar
James
J
Groves
Timothy
T
Zhou
Wenzhong
W
Grinshtein
Natalie
N
Parsons
Robin
R
Evelegh
Carole
C
Xing
Zhou
Z
Wan
Yonghong
Y
Bramson
Jonathan
J
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*
D015704:CD4 Antigens; D016207:Cytokines; D014765:Viral Vaccines