rdf:type |
|
lifeskim:mentions |
|
pubmed:issue |
12
|
pubmed:dateCreated |
1999-12-20
|
pubmed:abstractText |
BALB/c mice are susceptible to progressive infection with Leishmania major due to the preferential development of CD4(+) T cells that secrete Th2 cytokines. Although Th2 cell development and susceptibility are disrupted by blockade of CD86 function early in infection, CD28-deficient BALB/c mice remain susceptible to leishmaniasis. We therefore examined whether the alternative CD86 ligand, CTLA4, contributes to the expression of susceptibility. BALB/c mice treated for 2 weeks of infection with anti-CTLA4 monoclonal antibody developed more rapidly progressive disease than sham-treated mice, whereas normally resistant C57BL/6 mice were unaffected. The draining lymph node cells of anti-CTLA4-treated BALB/c mice produced up to sixfold more interleukin-4 (IL-4) and IL-13 than control mice in the first 2 weeks of infection, but IFN-gamma synthesis was reciprocally decreased. Anti-CTLA4 treatment of BALB/c mice pretreated with neutralizing anti-IL-4 antibody or genetically deficient in IL-4 also caused significant worsening of leishmaniasis. Exacerbation in IL-4 KO mice was associated with increased IL-13 and decreased gamma interferon (IFN-gamma) and inducible nitric oxide synthase (iNOS) mRNA expression in vivo. These data indicate that anti-CTLA4 antibody induced earlier and more-polarized Th2 responses in susceptible BALB/c mice infected with L. major. The mechanism of disease worsening was partially IL-4 independent, indicating that increased IL-13 and/or decreased IFN-gamma production may have disrupted nitric oxide-based microbicidal responses. We conclude that CTLA4 significantly modulates Th2 development in murine leishmaniasis and that the Th2-polarizing effects of anti-CTLA4 treatment result in IL-4-independent exacerbation of disease.
|
pubmed:grant |
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-10229856,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-10352289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-1334116,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-1717284,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-2521244,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-3079789,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-7481803,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-7523517,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-7534215,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-7543139,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-7543510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-7584144,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-7608551,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-7612219,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-7903102,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-8584936,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-8671638,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-8676075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-8760834,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-8940222,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9036947,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9064340,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9120387,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9126966,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9190944,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9221747,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9233595,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9317142,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9362525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9425733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9492006,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9529332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9531306,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9551948,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9600957,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9653096,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9653097,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9729043,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9780188,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9815271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9834101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9856949,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9856950,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9856951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9862358,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10569763-9916716
|
pubmed:language |
eng
|
pubmed:journal |
|
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/CTLA-4 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Ctla4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoconjugates,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/abatacept
|
pubmed:status |
MEDLINE
|
pubmed:month |
Dec
|
pubmed:issn |
0019-9567
|
pubmed:author |
|
pubmed:issnType |
Print
|
pubmed:volume |
67
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
6454-60
|
pubmed:dateRevised |
2011-11-17
|
pubmed:meshHeading |
pubmed-meshheading:10569763-Animals,
pubmed-meshheading:10569763-Mice,
pubmed-meshheading:10569763-Lymph Nodes,
pubmed-meshheading:10569763-Disease Susceptibility,
pubmed-meshheading:10569763-Female,
pubmed-meshheading:10569763-Leishmaniasis, Cutaneous,
pubmed-meshheading:10569763-Cells, Cultured,
pubmed-meshheading:10569763-Mice, Inbred BALB C,
pubmed-meshheading:10569763-Mice, Inbred C57BL,
pubmed-meshheading:10569763-Immunity, Innate,
pubmed-meshheading:10569763-Antibodies, Monoclonal,
pubmed-meshheading:10569763-Antigens, CD,
pubmed-meshheading:10569763-Cytokines,
pubmed-meshheading:10569763-Antigens, Differentiation,
pubmed-meshheading:10569763-Interleukin-4,
pubmed-meshheading:10569763-Mice, Knockout,
pubmed-meshheading:10569763-Th1 Cells,
pubmed-meshheading:10569763-Th2 Cells,
pubmed-meshheading:10569763-CTLA-4 Antigen
|