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Biomedical subjects

Robert W Carter

Publications and source records attributed to Robert W Carter.

7 recordsLinked to original sources
PubMed2006

Preferential induction of CD4+ T cell responses through in vivo targeting of antigen to dendritic cell-associated C-type lectin-1.

Targeting of Ags and therapeutics to dendritic cells (DCs) has immense potential for immunotherapy and vaccination. Because DCs are heterogeneous, optimal targeting strategies will require knowledge about functional specialization among DC subpopulations and identification of molecules for targeting appropriate DCs. We characterized the expression of a fungal recognition receptor, DC-associated C-type lectin-1 (Dectin-1), on mouse DC subpopulations and investigated the ability of an anti-Dectin-1 Ab to deliver Ag for the stimulation of immune responses. Dectin-1 was shown to be expressed on CD8alpha-CD4-CD11b+ DCs found in spleen and lymph nodes and dermal DCs present in skin and s.c. lymph nodes. Injection of Ag-anti-Dectin-1 conjugates induced CD4+ and CD8+ T cell and Ab responses at low doses where free Ag failed to elicit a response. Notably, qualitatively different immune responses were generated by targeting Ag to Dectin-1 vs CD205, a molecule expressed on CD8alpha+CD4-CD11b- DCs, dermal DCs, and Langerhans cells. Unlike anti-Dectin-1, anti-CD205 conjugates failed to elicit an Ab response. Moreover, when conjugates were injected i.v., anti-Dectin-1 stimulated a much stronger CD4+ T cell response and a much weaker CD8+ T cell response than anti-CD205. The results reveal Dectin-1 as a potential targeting molecule for immunization and have implications for the specialization of DC subpopulations.

Animals↗
PubMed2006

Induction of CD8+ T cell responses through targeting of antigen to Dectin-2.

Targeted delivery of antigens to dendritic cells (DC) can be used to optimise immunisation. We investigated whether the efficacy with which immune responses are induced can be improved by targeting Ags to a C-type lectin receptor, Dectin-2. When anti-Dectin-2 mAbs were injected s.c., mAb binding was detected on a low percentage of DC in the draining lymph node. Ag conjugated to anti-Dectin-2 mAbs was presented efficiently to CD8+ T cells in vivo and elicited CD8+ T cell responses at low doses where free Ag failed to induce a response. The results reveal Dectin-2 as a potential targeting molecule for immunisation.

Animals↗
PubMed2006

Salmonella typhimurium infection triggers dendritic cells and macrophages to adopt distinct migration patterns in vivo.

The presence of an anti-bacterial T cell response and evidence of bacterial products in inflamed joints of reactive arthritis patients suggests an antigen transportation role in this disease for macrophages and dendritic cells. We have investigated the functional properties and in vivo migration of macrophages and DC after infection with Salmonella enterica serovar Typhimurium (S. typhimurium). BM-derived macrophages and DC displayed enhanced expression of costimulatory molecules (CD40 and CD86) and increased production of pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-12p40) and nitric oxide after infection. Upon adoptive transfer into mice, infected DC migrated to lymphoid tissues and induced an anti-Salmonella T cell response, whereas infected macrophages did not. Infection of DC with S. typhimurium was associated with strong up-regulation of the chemokine receptor CCR7 and acquisition of responsiveness to chemokines acting through this receptor. Moreover, S. typhimurium-infected CCR7-deficient DC were unable to migrate to lymph nodes after adoptive transfer, although they did reach the spleen. Our data demonstrate distinct roles for macrophages and DC as antigen transporters after S. typhimurium infection and a dependence on CCR7 for migration of DC to lymph nodes after bacterial infection.

Animals↗
PubMed2004

Fully functional HLA B27-restricted CD4+ as well as CD8+ T cell responses in TCR transgenic mice.

The strong association of HLA B27 with spondyloarthropathies contrasts strikingly with most autoimmune diseases, which are HLA class II associated and thought to be mediated by CD4+ T lymphocytes. By introducing a human-derived HLA B27-restricted TCR into HLA B27 transgenic mice, we have obtained a functional TCR transgenic model, GRb, dependent on HLA B27 for response. Surprisingly, HLA B27 supported CD4+ as well as CD8+ T cell responses in vivo and in vitro. Further, HLA B27-restricted CD4+ T cells were capable of differentiation into a range of Th1 and Th2 T cell subsets with normal patterns of cytokine expression. The transgenic T cells were also able to enhance clearance of recombinant vaccinia virus containing influenza nucleoprotein in vivo. This is the first description of a human HLA class I-restricted TCR transgenic line. The existence of CD4+ MHC class I-restricted T cells has significant implications for immune regulation in autoimmunity and, in particular, in HLA B27-associated arthritis. We believe that this model provides a novel system for the study of unusual T cell behavior in vivo.

Animals↗
PubMed2004

Cloning of anthozoan fluorescent protein genes.

Many cnidarians display vivid fluorescence under proper lighting conditions. In general, these colors are due to the presence of fluorescent proteins similar to the green fluorescent protein (GFP) originally isolated from the hydrozoan medusa Aequorea victoria (Cnidaria: Hydrozoa). To optimize the search for new fluorescent proteins (FPs), a technique was developed that allows for the rapid cloning and screening of FP genes without the need for a prior knowledge of gene sequence. Using this method, four new FP genes were cloned, a green from Montastraea cavernosa (Anthozoa: Scleractinia: Faviidae), a cyan from Pocillopora damicornis (Anthozoa: Scleractinia: Pocilloporidae), a cyan from Discosoma striata (Anthozoa: Corallimorpharia), and a red from a second Discosoma species. Two additional green FPs were cloned, one from M. cavernosa and one from its congener Montastraea faveolata, from purified cDNA using PCR primers designed for the first M. cavernosa green FP. Each FP has recognizable amino acid sequence motifs that place them conclusively in the GFP protein family. Mutation of these products using a low-stringency PCR protocol followed by screening of large numbers of bacterial colonies allowed rapid creation of mutants with a variety of characteristics, including changes in color, maturation time, and brightness. An enhanced version of the new red FP, DspR1+, matures faster at 30 degrees C than the commercially available DsRed but matures slower than DsRed at 37 degrees C. One of the M. cavernosa green FPs, McaG2, is highly resistant to photobleaching and has a fluorescence quantum yield approximately twice that of EGFP-1.

Amino Acid Sequence↗
PubMed2004

Severe lactic acidosis in association with reverse transcriptase inhibitors with potential response to L-carnitine in a pediatric HIV-positive patient.

We report a case of life-threatening lactic acidosis in a 10-year-old male with HIV stage B2 infection, presumed to be vertically acquired. This occurred after several months of therapy with d4t, ddl, and nevirapine. His most recent CD4 count was 347 cells per microliter and viral load 16,000 copies per milliliter 3 weeks prior to admission. The peak lactic acid level was 12.4 mmol/L. Although multiple therapeutic interventions took place, the patient showed rapid improvement and resolution temporally associated with the administration of levocarnitine.

Acidosis, Lactic↗