Recruitment of different subsets of antigen-presenting cells selectively modulates DNA vaccine-elicited CD4+ and CD8+ T lymphocyte responses.
The immunogenicity of plasmid DNA vaccines may be limited by the availability of professional antigen-presenting cells (APC) at the site of inoculation. Here we demonstrate that the types of APC recruited to the injection site can selectively modulate CD4(+) or CD8(+) T lymphocyte responses elicited by an HIV-1 Env DNA vaccine in mice. Coadministration of plasmid GM-CSF with the DNA vaccine resulted in the recruitment of macrophages to the site of inoculation and specifically augmented vaccine-elicited CD4(+) T lymphocyte responses. In contrast, coadministration of plasmid MIP-1 alpha with the DNA vaccine resulted in the recruitment of dendritic cells to the injection site and enhanced vaccine-elicited CD8(+) T lymphocyte responses. Interestingly, coadministration of both plasmid GM-CSF and plasmid MIP-1 alpha with the DNA vaccine recruited both macrophages and dendritic cells and led to a synergistic and sustained augmentation of CD4(+)and CD8(+) T lymphocyte responses. These data demonstrate the critical importance of locally recruited professional APC in determining the magnitude and nature of immune responses elicited by plasmid DNA vaccines. Moreover, these studies show that different subsets of professional APC can selectively modulate DNA vaccine-elicited T lymphocyte responses.
McKay
Paul F
PF
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston 02215, USA.
Barouch
Dan H
DH
Santra
Sampa
S
Sumida
Shawn M
SM
Jackson
Shawn S
SS
Gorgone
Darci A
DA
Lifton
Michelle A
MA
Letvin
Norman L
NL
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D054407:Chemokine CCL4; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000276:immunology; D051379:Mice; D019444:Vaccines, DNA / Q000276:immunology*
D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D019444:Vaccines, DNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor