Gene/Protein
Disease
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Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Target Concepts:
Gene/Protein
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Enzyme
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Query: UMLS:C0024530 (
malaria
)
44,886
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Dendritic cells (DC) play a pivotal role in the induction and regulation of immune responses, including the induction of cytotoxic T lymphocytes (CTL) responses. These are essential for the eradication of cancers and pathogens including HIV and
malaria
, for which there are currently no effective vaccines. New developments in our understanding of DC biology have identified the key DC subset responsible for CTL induction, which is now an attractive candidate to target for vaccination. These DC are characterized by expression of novel markers Clec9A and
XCR1
, and a specialized capacity to cross-present antigen (Ag) from tumors and pathogens that do not directly infect DC. New generation DC vaccines that specifically target the cross-presenting DC in vivo have already demonstrated potential in preclinical animal models but the challenge remains to translate these findings into clinically efficacous vaccines in man. This has been greatly facilitated by the recent identification of the equivalent Clec9A(+)
XCR1
(+) cross-presenting DC in human lymphoid tissues and peripheral tissues that are key sites for vaccination administration. These findings combined with further studies on DC subset biology have important implications for the design of new CTL-mediated vaccines.
...
PMID:New generation of dendritic cell vaccines. 2329 51
We describe an MHC class II (I-A
b
)-restricted TCR transgenic mouse line that produces CD4
+
T cells specific for
Plasmodium
species. This line, termed PbT-II, was derived from a CD4
+
T cell hybridoma generated to blood-stage
Plasmodium berghei
ANKA (PbA). PbT-II cells responded to all
Plasmodium
species and stages tested so far, including rodent (PbA,
P. berghei
NK65,
Plasmodium chabaudi
AS, and
Plasmodium yoelii
17XNL) and human (
Plasmodium falciparum
) blood-stage parasites as well as irradiated PbA sporozoites. PbT-II cells can provide help for generation of Ab to
P. chabaudi
infection and can control this otherwise lethal infection in CD40L-deficient mice. PbT-II cells can also provide help for development of CD8
+
T cell-mediated experimental cerebral
malaria
(ECM) during PbA infection. Using PbT-II CD4
+
T cells and the previously described PbT-I CD8
+
T cells, we determined the dendritic cell (DC) subsets responsible for immunity to PbA blood-stage infection. CD8
+
DC (a subset of
XCR1
+
DC) were the major APC responsible for activation of both T cell subsets, although other DC also contributed to CD4
+
T cell responses. Depletion of CD8
+
DC at the beginning of infection prevented ECM development and impaired both Th1 and follicular Th cell responses; in contrast, late depletion did not affect ECM. This study describes a novel and versatile tool for examining CD4
+
T cell immunity during
malaria
and provides evidence that CD4
+
T cell help, acting via CD40L signaling, can promote immunity or pathology to blood-stage
malaria
largely through Ag presentation by CD8
+
DC.
...
PMID:Development of a Novel CD4
+
TCR Transgenic Line That Reveals a Dominant Role for CD8
+
Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria. 2908 38
