PMID- 11070014
OWN - NLM
STAT- MEDLINE
DCOM- 20001204
LR  - 20190508
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 74
IP  - 23
DP  - 2000 Dec
TI  - DNA vaccines encoding interleukin-8 and RANTES enhance antigen-specific Th1-type 
      CD4(+) T-cell-mediated protective immunity against herpes simplex virus type 2 in 
      vivo.
PG  - 11173-80
AB  - Chemokines are inflammatory molecules that act primarily as chemoattractants and 
      as activators of leukocytes. Their role in antigen-specific immune responses is 
      of importance, but their role in disease protection is unknown. Recently it has 
      been suggested that chemokines modulate immunity along more classical Th1 and Th2 
      phenotypes. However, no data currently exist in an infectious challenge model 
      system. We analyzed the modulatory effects of selected chemokines (interleukin-8 
      [IL-8], gamma interferon-inducible protein 10 [IP-10], RANTES, monocyte 
      chemotactic protein 1 [MCP-1], and macrophage inflammatory protein 1 alpha [MIP-1 
      alpha]) on immune phenotype and protection against lethal challenge with herpes 
      simplex virus type 2 (HSV-2). We observed that coinjection with IL-8 and RANTES 
      plasmid DNAs dramatically enhanced antigen-specific Th1 type cellular immune 
      responses and protection from lethal HSV-2 challenge. This enhanced protection 
      appears to be mediated by CD4(+) T cells, as determined by in vitro and in vivo 
      T-cell subset deletion. Thus, IL-8 and RANTES cDNAs used as DNA vaccine adjuvants 
      drive antigen-specific Th1 type CD4(+) T-cell responses, which result in reduced 
      HSV-2-derived morbidity, as well as reduced mortality. However, coinjection with 
      DNAs expressing MCP-1, IP-10, and MIP-1 alpha increased mortality in the 
      challenged mice. Chemokine DNA coinjection also modulated its own production as 
      well as the production of cytokines. These studies demonstrate that chemokines 
      can dominate and drive immune responses with defined phenotypes, playing an 
      important role in the generation of protective antigen-specific immunity.
FAU - Sin, J
AU  - Sin J
AD  - Department of Pathology and Laboratory Medicine, University of Pennsylvania, 
      Philadelphia, Pennsylvania 19104, USA.
FAU - Kim, J J
AU  - Kim JJ
FAU - Pachuk, C
AU  - Pachuk C
FAU - Satishchandran, C
AU  - Satishchandran C
FAU - Weiner, D B
AU  - Weiner DB
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Chemokine CCL5)
RN  - 0 (Cytokines)
RN  - 0 (Herpesvirus Vaccines)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Interleukin-8)
RN  - 0 (Vaccines, DNA)
RN  - 0 (Viral Vaccines)
SB  - IM
MH  - Animals
MH  - Chemokine CCL5/genetics/*immunology
MH  - Cytokines/biosynthesis
MH  - Female
MH  - Herpesvirus 2, Human/*immunology
MH  - Herpesvirus Vaccines/*immunology
MH  - Immunoglobulin G/biosynthesis
MH  - Interleukin-8/genetics/*immunology
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Th1 Cells/*immunology
MH  - Th2 Cells/immunology
MH  - Vaccines, DNA/*immunology
MH  - Viral Vaccines/*immunology
PMC - PMC113206
EDAT- 2000/11/09 11:00
MHDA- 2001/02/28 10:01
PMCR- 2000/12/01
CRDT- 2000/11/09 11:00
PHST- 2000/11/09 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/11/09 11:00 [entrez]
PHST- 2000/12/01 00:00 [pmc-release]
AID - 0006 [pii]
AID - 10.1128/jvi.74.23.11173-11180.2000 [doi]
PST - ppublish
SO  - J Virol. 2000 Dec;74(23):11173-80. doi: 10.1128/jvi.74.23.11173-11180.2000.