The dendritic cell-specific chemokine, dendritic cell-derived CC chemokine 1, enhances protective cell-mediated immunity to murine malaria.
Cell-mediated immunity plays a crucial role in the control of many infectious diseases, necessitating the need for adjuvants that can augment cellular immune responses elicited by vaccines. It is well established that protection against one such disease, malaria, requires strong CD8(+) T cell responses targeted against the liver stages of the causative agent, Plasmodium spp. In this report we show that the dendritic cell-specific chemokine, dendritic cell-derived CC chemokine 1 (DC-CK1), which is produced in humans and acts on naive lymphocytes, can enhance Ag-specific CD8(+) T cell responses when coadministered with either irradiated Plasmodium yoelii sporozoites or a recombinant adenovirus expressing the P. yoelii circumsporozoite protein in mice. We further show that these enhanced T cell responses result in increased protection to malaria in immunized mice challenged with live P. yoelii sporozoites, revealing an adjuvant activity for DC-CK1. DC-CK1 appears to act preferentially on naive mouse lymphocytes, and its adjuvant effect requires IL-12, but not IFN-gamma or CD40. Overall, our results show for the first time an in vivo role for DC-CK1 in the establishment of primary T cell responses and indicate the potential of this chemokine as an adjuvant for vaccines against malaria as well as other diseases in which cellular immune responses are important.
Bruna-Romero
Oscar
O
Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010, USA.
Schmieg
John
J
Del Val
Margarita
M
Buschle
Michael
M
Tsuji
Moriya
M
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000502:physiology*; D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019742:Chemokines, CC / Q000008:administration & dosage / Q000276:immunology / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010967:Plasmodium yoelii / Q000235:genetics / Q000254:growth & development / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; C111792:CCL18 protein, human; D019742:Chemokines, CC; D017780:Malaria Vaccines; D014614:Vaccines, Synthetic; D018664:Interleukin-12