385,872 research outputs found
L-arginine deprivation impairs Leishmania major-specific T-cell responses.
No full textThe amino acid L-arginine plays a crucial role in the regulation of immune responses. We have recently shown that uncontrolled replication of Leishmania parasites at the site of pathology correlates with high levels of arginase activity in nonhealing leishmaniasis and that this elevated arginase activity causes local depletion of L-arginine. To further our understanding of the impact of L-arginine deprivation in experimental leishmaniasis, here we characterize in detail the effects of L-arginine deprivation on antigen-specific T cells and MPhi. The results of our study show that decrease of L-arginine levels in the extracellular milieu affects the biological activities of Leishmania major-specific T cells, both at the level of the magnitude and the quality of their responses. L. major-specific CD4(+) T cells rendered hyporesponsive by L-arginine deprivation can be partially rescued by addition of exogenous L-arginine to produce IL-4 and IL-10, but not to produce IFN-gamma. Furthermore, our results show that L-arginine deprivation also greatly impacts parasite growth in activated macrophages. In summary, our results suggest that L-arginine levels affect both Th cell responses and parasite replication
Les Ruines de Paestum, ou de Posidonie, dans la Grande Grèce, par T. Major,... traduit de l'anglais
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T helper1/T helper2 cells and resistance/susceptibility to Leishmania infection : is this paradigm still relevant?
No full textWork in large part on Leishmania major in the 1980s identified two distinct apparently counter-regulatory CD4 T cell populations, T helper (h)1 and Th2, that controlled resistance/susceptibility to infection respectively. However, the generation of IL-4mice in the 1990s questioned the paramount role of thisTh2 archetypal cytokine in the non-healing response to Leishmania infection. The more recent characterization of CD4 T cell regulatory populations and further effector CD4 T helper populations, Th17, Th9, and T follicular (f)h cells as well as the acknowledged plasticity in T helper cell function has further added to the complexity of host pathogen interactions.These interactions are complicated by the multiplicity of cells that respond to CD4 T cell subset signatory cytokines, as well as the diversity of Leishmania species that are often subject to significantly different immuneregulatory controls. In this article we review current knowledge with regard to the role of CD4 T cells and their products during Leishmania infection. In particular we update on our studies using conditional IL-4Rα gene-deficient mice that have allowed dissection of the cell interplay dictating the disease outcomes of the major Leishmania species infecting humans
T-cell epitopes of the major peach allergen, Pru p 3: Identification and differential T-cell response of peach-allergic and non-allergic subjects
No full textLipid transfer proteins (LTPs), particularly peach Pru p 3, are the most relevant plant food allergens in the South of Europe, and, therefore, their allergic properties have been extensively studied. However, neither T-cell epitopes nor their effect on the patients’ T-cell response has been investigated in any member of the LTP panallergen family. The objective of the present study was to map the major T-cell epitopes of Pru p 3, as well as to evaluate their induced T-cell response in peach-allergic versus control subjects. Thus, peripheral blood mononuclear cells (PBMCs) from 18 peach-allergic patients and Pru p 3-specific T-cell lines (TCLs) from 9 of them were cultured with Pru p 3 and with a panel of 17 derived peptides (10-mer overlapping in 5 amino acids representing the full sequence of Pru p 3). Proliferation in 5-day assays was carried out via tritiated-thymidine incorporation, while IL4 and IFNγ production was assessed via sandwich enzyme-linked immunosorbent tests (ELISA) of TCL culture supernatants. The results were compared to those obtained from 10 non-peach allergic control volunteers. Two consecutive peptides showed the highest activation capacity. About 74% of PBMCs and TCLs recognized them, forming a single T-epitope: Pru p 365–80. Additionally, other specific T-cell epitopes were observed. Pru p 325–35 was detected by more than 60% of TCLs from peach-allergic patients, and Pru p 345–55 only activated PBMCs from control subjects. Interestingly, TCLs from patients were associated with a Th2-type, whereas control TCLs presented a Th1-type cytokine response. The major immunogenic T-cell epitope identified in Pru p 3, Pru p 365–80, is a good candidate to develop new vaccines for hypersensitivity reactions associated with LTP allergens from Rosaceae fruits
Rapid and long-term disappearance of CD4+ T lymphocyte responses specific for Anaplasma marginale major surface protein-2 (MSP2) in MSP2 vaccinates following challenge with live A. marginale
No full textIn humans and ruminants infected with Anaplasma, the major surface protein 2 (MSP2) is immunodominant. Numerous CD4(+) T cell epitopes in the hypervariable and conserved regions of MSP2 contribute to this immunodominance. Antigenic variation in MSP2 occurs throughout acute and persistent infection, and sequentially emerging variants are thought to be controlled by variant-specific Ab. This study tested the hypothesis that challenge of cattle with Anaplasma marginale expressing MSP2 variants to which the animals had been immunized, would stimulate variant epitope-specific recall CD4(+) T cell and IgG responses and organism clearance. MSP2-specific T lymphocyte responses, determined by IFN-gamma ELISPOT and proliferation assays, were strong before and for 3 wk postchallenge. Surprisingly, these responses became undetectable by the peak of rickettsemia, composed predominantly of organisms expressing the same MSP2 variants used for immunization. Immune responsiveness remained insignificant during subsequent persistent A. marginale infection up to 1 year. The suppressed response was specific for A. marginale, as responses to Clostridium vaccine Ag were consistently observed. CD4(+)CD25(+) T cells and cytokines IL-10 and TGF-beta1 did not increase after challenge. Furthermore, a suppressive effect of nonresponding cells was not observed. Lymphocyte proliferation and viability were lost in vitro in the presence of physiologically relevant numbers of A. marginale organisms. These results suggest that loss of memory T cell responses following A. marginale infection is due to a mechanism other than induction of T regulatory cells, such as peripheral deletion of MSP2-specific T cells
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
[Major J. T. Whitfield, Confederate States Army]
No full textPortrait of Major J. T. Whitfield, 27th Texas Cavalry, Confederate States Army.Verso: [handwritten] J. T. Whitfield, son of Gen. J. W. Whitfield (Uncle Tommy) [stamped imprint] L. I. Prince, Photographer, 112 Canal and 8 St. Charles Sts., corner building, over Union Insurance Co., New Orleans. Additional Copies can be had when required
Letter from Major Sims to John T. Cunningham, on behalf of Senator W.E. Brock, 1930-01-06
No full textA typed letter from Senator Brock's secretary, Major Sims in Washington, D.C. to John T. Cunningham in Clarksville, Tennessee. On behalf of Senator Brock, Major Sims is thanking Cunningham for his letter in regards to Charles Hanratty. Sims assures Cunningham it will be brought to Senator Brock's attention hen he returns to his office
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