Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For analysis of the role of immune T cells in protective immunity against murine malaria, Plasmodium yoelii-immune Lyt T-cell subsets were functionally characterized in vitro and in vivo. Selected Lyt2- and Lyt2+ T cells from P. yoelii-immune C57BL/10 mice differed in their capability to proliferate in response to P. yoelii antigen in vitro. Only the Lyt2- T-cell population produced T-cell growth factor upon restimulation, and none of the selected T-cell subsets produced detectable amounts of macrophage activating factor. Lyt2- but not Lyt2+ lymphocytes were capable of transferring protection to normal C57BL/10 mice. When transferred into T-cell-deficient C57BL/6-nu/nu mice, adoptive resistance to P. yoelii by Lyt2- lymphocytes was only demonstrable after prior reconstitution of recipients with normal T cells. These results suggest an interaction between P. yoelii-immune Lyt2- T cells and normal T lymphocytes via T-cell growth factor in the development of protective immunity to malaria.
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PMID:T-cell-mediated immune response in murine malaria: differential effects of antigen-specific Lyt T-cell subsets in recovery from Plasmodium yoelii infection in normal and T-cell-deficient mice. 285 83

Current malaria vaccine strategies focus on subunit vaccines that contain one or a limited number of malaria Ag. However, there is widespread nonresponsiveness to many of these Ag probably resulting from Ir gene control. Using a congenic mouse model, we demonstrated that human rIL-2 (as an adjuvant) can overcome Ir gene controlled low immune responsiveness to peptide malaria Ag vaccine candidates [R32tet32, R32LR, and Th2R-NP (NANP)5NA] as determined by the antibody response, providing it is emulsified with the Ag during immunization. This effect is not caused by IL-2 merely acting as a foreign protein and stimulating noncognate help; it requires biologic activity of the IL-2, as determined by studying the effect of inactive rIL-2, which has minimal biologic activity but which has retained its antigenicity. IL-2 does not appear to be working by an effect on priming of specific Th, and IL-2 cannot overcome an Ir gene controlled low T cell proliferative response. IL-2 may have a role to play in human vaccine development where a high titer antibody response to a subunit vaccine is required.
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PMID:Recombinant human IL-2 overcomes genetic nonresponsiveness to malaria sporozoite peptides. Correlation of effect with biologic activity of IL-2. 296 96

Patients with acute Plasmodium falciparum malaria have defective cell-mediated immune responses to malaria-specific Ag (MA). This immunologic defect may partially explain the difficulty with which natural immunity to falciparum malaria develops and may have important implications for the efficacy of potential malaria vaccines in endemic areas. To investigate the basis of this immune defect, we have examined the capacity of PBMC from patients with acute falciparum malaria to produce IL-2 and to express I1-2R in response to Ag stimulation. The effect of exogenous IL-1 and IL-2 on lymphocyte proliferation was studied. Soluble IL-2R levels were measured in acute and convalescent sera. Our results showed that no detectable IL-2 was produced and no IL-2R were expressed by PBMC in response to MA during the acute infection. IL-2 production and IL-2R expression were also depressed when PBMC were exposed to streptococcal Ag. The specific immune defect was not reconstituted by the addition of graded doses of purified human IL-1 or IL-2 and could not be attributed to suppressor adherent cells. In contrast to the absence of IL-2 and cell-bound IL-2R, circulating soluble IL-2R was elevated in acute sera. These findings suggest that the lack of IL-2, through either a defect in its production or inhibition of its activity, may be the basis of the Ag-specific immune unresponsiveness in acute P. falciparum malaria.
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PMID:Defective production of and response to IL-2 in acute human falciparum malaria. 297 29

T cell-dependent, cell-mediated immune mechanisms have been shown to contribute to resistance against malaria. Because the identity of plasmodial Ag responsible for the activation of these protective immune responses remains unknown, a major step in isolating these potential immunizing agents will be the development of adequate screening procedures designed to identify important T cell Ag. This study focused on the isolation of protective T cell clones that may play a pivotal role in this process. A T cell clone designated CTR2.1 and two subclones derived from it adoptively transferred protection to athymic nude mice infected with Plasmodium chabaudi adami, a murine malarial parasite known to be recognized by protective thymus-dependent immune mechanisms. The protective T cell clone displayed a L3T4+, Lyt-2- surface phenotype and secreted both IFN-gamma and IL-2 after stimulation with solubilized parasites in vitro. This is the first report of results demonstrating a cloned T cell line capable of providing adoptive protection against malaria in vivo. More importantly, CTR2.1 and other protective T cell clones may provide for the identification of plasmodial antigenic epitopes recognized by important cell-mediated immune mechanisms during acute malarial infection.
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PMID:Adoptive protection against Plasmodium chabaudi adami malaria in athymic nude mice by a cloned T cell line. 312 38

The molecular characteristics of a serum IL-2 inhibitor were determined by fractionating active sera from normal and malaria-infected mice, and assaying inhibitory activity in blocking production and expression of IL-2 activity. Using isoelectric focusing and ion exchange chromatography, the activity resolved in a single peak (pI = 6.2). HPLC gel filtration resolved two peaks of activity (50,000 and 25,000 MW) which are probably related. The molecule is precipitated by 50% saturated ammonium sulphate, and is destroyed by heating above 56 degrees or by acidification below pH 4.
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PMID:Serum IL-2 inhibitor in mice. II. Molecular characteristics. 387 70

V gamma 9+ T cells from malaria non-exposed donors make proliferative responses to Plasmodium falciparum on in vitro stimulation. V gamma 9+ cells are strongly activated by components of the schizont stage of the parasite and by antigens released into the culture upon schizogony, while CD4+V gamma 9- cells are stimulated by the earlier stages of the parasite. Using reverse transcriptase-polymerase chain reaction (RT-PCR) we determined mRNA expression for 14 cytokines in highly purified V gamma 9+ cells enriched by positive selection after in vitro stimulation with P. falciparum schizont antigens. Interferon-gamma (IFN-gamma) and Tumor Necrosis Factor-alpha (TNF-alpha) were detected in all samples tested. The majority of samples also expressed TNF-beta, transforming growth factor-beta (TGF-beta) and Interleukin-8 (IL-8). Only occasional samples expressed IL-2, IL-5 and IL-10. Using the ELISPOT assay we found that a large fraction of the reactive V gamma 9+ cells produced IFN-gamma and that gamma delta T cells are the major producers of IFN-gamma in cultures stimulated with schizont antigens. The majority of V gamma 9+ cells in these cultures also express the membrane-bound form of TNF-alpha. Expression of these cytokines speaks for a cytolytic and/or inflammatory role of gamma delta cells in the response to malaria in non-exposed individuals.
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PMID:Cytokine profiles for human V gamma 9+ T cells stimulated by Plasmodium falciparum. 750 22

The expression of selected interleukin receptors by cloned CD4+ T cells specific for the murine malaria parasite Plasmodium chabaudi chabaudi (P. chabaudi) representative of the T-helper (Th) 1 and Th2 subsets was examined. Both sets of clones expressed receptors for those interleukins for which they had a growth factor requirement in vitro. Each Th1 clone expressed receptors for, and was responsive to, interleukin (IL)-2 and IL-4, while each Th2 clone expressed receptors for, and was responsive to, IL-2, IL-4 and IL-1. IL-1 receptor (IL-1R) expression by the Th1 clones was either negligible or could not be detected. The disparity in expression of IL-1R by the Th1 and Th2 clones was more clear-cut than has been previously reported and IL-1R provided a definitive phenotypic marker for clones of the Th2 subset. Should IL-1R expression prove to be a feature of other Th2 cells cultured long-term in vitro, this will be invaluable for investigations involving the phenotyping, depletion or selection of CD4+ T cells of either Th1 or Th2 subset.
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PMID:Expression of the IL-1 receptor discriminates Th2 from Th1 cloned CD4+ T cells specific for Plasmodium chabaudi. 751 28

In vivo interleukin (IL)-2, IL-4, IL-10, and interferon (IFN)-gamma production was measured at the mRNA transcript and protein levels in patients acutely infected with Plasmodium falciparum and during convalescence. Both IL-10 and IFN-gamma but not IL-2 were produced regardless of the patients' clinical severity. IL-4 production was variable. Circulating IFN-gamma and IL-10 were significantly higher in patients with severe disease (P < .01 and .001, respectively). In vitro stimulation of peripheral blood mononuclear cells (PBMC) by malarial antigens during acute infection showed that although there was no lymphoproliferation, the cells could produce IL-10 and IFN-gamma. Recombinant human IL-10 completely abolished in vitro tumor necrosis factor (TNF)-alpha production in response to malarial antigens, as well as the antigen-specific proliferative response of convalescent patients. However, anti-IL-10 was insufficient to restore proliferation of PBMC from acutely infected patients. These findings suggest that IL-10 may have an important negative feedback action on the production of inflammatory cytokines in acute falciparum malaria without contributing to the defect in antigen-specific proliferation.
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PMID:Interleukin-10 inhibits tumor necrosis factor production but not antigen-specific lymphoproliferation in acute Plasmodium falciparum malaria. 765 79

In order to describe presumed paediatric malaria on a cell-immunological basis, the soluble receptors of IL-2 (sIL-2R) and tumour necrosis factor (sTNF-R55 and sTNF-R75) were quantified in highly exposed young Tanzanian children. Sera were obtained from 66 acute and 72 reported febrile patients during health post consultations and follow-ups and from 68 community controls. Levels of sIL-2R, sTNF-R55 and sTNF-R75 were significantly elevated during fever attacks, especially in very young children. Soluble TNF-R75 levels were most stable and those of sTNF-R55 least. Levels of sTNF-R55 were related to the magnitude of fever and thus appeared to reflect attack severity. Levels of sTNF-R75 were highly significantly associated with parasite density, indicating that this response is malaria-specific. The present study indicates that sTNF-R75 levels could become a useful immunological tool in malaria intervention studies, as they reflect changes in malaria-specific immune responses. Future studies should validate this potential in different endemic settings.
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PMID:Immunological markers of childhood fevers in an area of intense and perennial malaria transmission. 769 24

Both antibody-dependent and antibody-independent mechanisms are involved in immune protection against the asexual blood stages of the malaria parasite. It is well established that T cells play a crucial role in both induction and maintenance of this immunity. Of the two T-cell subsets (CD4+, CD8+) carrying alpha/beta T-cell receptors, the CD4+ T cells are of major importance for the development of blood stage immunity in both experimental and human malaria. In mice, CD4+ T cells comprise at least two functionally distinct cell types (TH1, TH2), distinguished on the basis of their lymphokine production. The balance between these subsets is critical for the outcome of an infection. In some rodent malarias, TH1 cells producing IFN-gamma and IL-2 are important for controlling infection in its early phases, while TH2 cells, producing i.a. IL-4 and IL-10, together with antibodies, are important for parasite clearance in later phases of infection. Distinct CD4+ T cells of either TH1 or TH2 type also have regulatory functions in human P. falciparum infection. In contrast to the CD4+ T cells, the role of CD8+ T cells in blood stage infection appears to be limited, but suppression of some CD4+ activities has been reported for both experimental and human malaria. As in other infections, peripheral T cells equipped with gamma/delta receptors are strongly upregulated in malaria and also respond to parasite antigens in vitro by proliferation and lymphokine production. However, the importance of the gamma/delta T cells for protection when compared with pathogenesis is presently unclear. Rapid advances made in recent years in the characterization and cloning of plasmodial antigens eliciting immune protection have made it possible to define some of the antigenic structures involved in T-cell immunity. This, together with an improved understanding of cellular mechanisms, provides some basis for the development of modern malaria vaccines.
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PMID:T-cell control of immunity to the asexual blood stages of the malaria parasite. 770 48


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