Navegando por Palavras-chave "CD8"

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    Importance of CD8 T cell-mediated immune response during intracellular parasitic infections and its implications for the development of effective vaccines
    (Academia Brasileira de Ciências, 2003-12-01) Rodrigues, Mauricio Martins [UNIFESP]; Boscardin, Silvia Beatriz [UNIFESP]; Vasconcelos, Jose Ronnie Carvalho de [UNIFESP]; Hiyane, Meire Ioshie [UNIFESP]; Salay, Gerson [UNIFESP]; Soares, Irene S.; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Obligatory intracellular parasites such as Plasmodium sp, Trypanosoma cruzi, Toxoplasma gondii and Leishmania sp are responsible for the infection of hundreds of millions of individuals every year. These parasites can deliver antigens to the host cell cytoplasm that are presented through MHC class I molecules to protective CD8 T cells. The in vivo priming conditions of specific CD8 T cells during natural infection are largely unknown and remain as an area that has been poorly explored. The antiparasitic mechanisms mediated by CD8 T cells include both interferon-g-dependent and -independent pathways. The fact that CD8 T cells are potent inhibitors of parasitic development prompted many investigators to explore whether induction of these T cells can be a feasible strategy for the development of effective subunit vaccines against these parasitic diseases. Studies performed on experimental models supported the hypothesis that CD8 T cells induced by recombinant viral vectors or DNA vaccines could serve as the basis for human vaccination. Regimens of immunization consisting of two different vectors (heterologous prime-boost) are much more efficient in terms of expansion of protective CD8 T lymphocytes than immunization with a single vector. The results obtained using experimental models have led to clinical vaccination trials that are currently underway.
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    Lower numbers of circulating natural killer T (NK T) cells in individuals with human T lymphotropic virus type 1 (HTLV-1) associated neurological disease
    (Wiley-Blackwell, 2009-12-01) Ndhlovu, L. C.; Snyder-Cappione, J. E.; Carvalho, Karina Inacio [UNIFESP]; Leal, F. E.; Loo, C. P.; Bruno, F. R.; Jha, A. R.; Devita, D.; Hasenkrug, A. M.; Barbosa, H. M. R. [UNIFESP]; Segurado, A. C.; Nixon, D. F.; Murphy, E. L.; Kallas, Esper Georges [UNIFESP]; Univ Calif San Francisco; Blood Syst Res Inst; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Human T lymphotropic virus type 1 (HTLV-1) infects 10-20 million people worldwide. the majority of infected individuals are asymptomatic; however, approximately 3% develop the debilitating neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is also currently no cure, vaccine or effective therapy for HTLV-1 infection, and the mechanisms for progression to HAM/TSP remain unclear. NK T cells are an immunoregulatory T cell subset whose frequencies and effector functions are associated critically with immunity against infectious diseases. We hypothesized that NK T cells are associated with HAM/TSP progression. We measured NK T cell frequencies and absolute numbers in individuals with HAM/TSP infection from two cohorts on two continents: São Paulo, Brazil and San Francisco, CA, USA, and found significantly lower levels when compared with healthy subjects and/or asymptomatic carriers. Also, the circulating NK T cell compartment in HAM/TSP subjects is comprised of significantly more CD4(+) and fewer CD8(+) cells than healthy controls. These findings suggest that lower numbers of circulating NK T cells and enrichment of the CD4(+) NK T subset are associated with HTLV-1 disease progression.
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    Re-circulation of lymphocytes mediated by sphingosine-1-phosphate receptor-1 contributes to resistance against experimental infection with the protozoan parasite Trypanosoma cruzi
    (Elsevier B.V., 2012-04-16) Dominguez, Mariana Ribeiro [UNIFESP]; Ersching, Jonatan [UNIFESP]; Lemos, Ramon [UNIFESP]; Machado, Alexandre V.; Bruna-Romero, Oscar; Rodrigues, Mauricio Martins [UNIFESP]; Vasconcelos, Jose Ronnie Carvalho de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fiocruz MS; Universidade Federal de Minas Gerais (UFMG)
    T-cell mediated immune responses are critical for acquired immunity against infection by the intracellular protozoan parasite Trypanosoma cruzi. Despite its importance, it is currently unknown where protective T cells are primed and whether they need to re-circulate in order to exert their anti-parasitic effector functions. Here, we show that after subcutaneous challenge, CD11c(+)-dependent specific CD8(+) T-cell immune response to immunodominant parasite epitopes arises almost simultaneously in the draining lymph node (LN) and the spleen. However, until day 10 after infection, we observed a clear upregulation of activation markers only on the surface of CD11C(+)PDCA1(+) cells present in the LN and not in the spleen. Therefore, we hypothesized that CD8(+) T cells re-circulated rapidly from the LN to the spleen. We investigated this phenomenon by administering FTY720 to T. cruzi-infected mice to prevent egress of T cells from the LN by interfering specifically with signalling through sphingosine-1-phosphate receptor-1. in T. cruzi-infected mice receiving FTY720, CD8 T-cell immune responses were higher in the draining LN and significantly reduced in their spleen. Most importantly, FTY720 increased susceptibility to infection, as indicated by elevated parasitemia and accelerated mortality. Similarly, administration of FTY720 to mice genetically vaccinated with an immunodominant parasite antigen significantly reduced their protective immunity, as observed by the parasitemia and survival of vaccinated mice.We concluded that re-circulation of lymphocytes mediated by sphingosine-1-phosphate receptor-1 greatly contributes to acquired and vaccine-induced protective immunity against experimental infection with a human protozoan parasite. (C) 2012 Elsevier B.V. All rights reserved.
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    Strain-specific protective immunity following vaccination against experimental Trypanosoma cruzi infection
    (Elsevier B.V., 2009-09-18) Haolla, Filipe Augusto Bettencourt [UNIFESP]; Claser, Carla [UNIFESP]; Alencar, Bruna Cunha Gondim de [UNIFESP]; Tzelepis, Fanny [UNIFESP]; Vasconcelos, Jose Ronnie Carvalho de [UNIFESP]; Oliveira, Gabriel de; Silverio, Jaline Coutinho; Machado, Alexandre Vieira; Lannes-Vieira, Joseli; Bruna-Romero, Oscar; Gazzinelli, Ricardo Tostes; Santos, Ricardo Ribeiro dos; Soares, Milena Botelho Pereira; Rodrigues, Mauricio Martins [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fiocruz MS; Universidade Federal de Minas Gerais (UFMG); Univ Massachusetts; Hosp Sao Rafael
    Immunisation with Amastigote Surface Protein 2 (asp-2) and trans-sialidase (ts) genes induces protective immunity in highly susceptible A/Sn mice, against infection with parasites of the Y strain of Trypanosoma cruzi. Based on immunological and biological strain variations in T cruzi parasites, our goal was to validate our vaccination results using different parasite strains. Due to the importance of the CD8(+) T cells in protective immunity, we initially determined which strains expressed the immunodominant H-2K(k)-restricted epitope TEWETGQI. We tested eight strains, four of which elicited immune responses to this epitope (Y, G, Colombian and Colombia). We selected the Colombian and Colombia strains for our studies. A/Sn mice were immunised with different regimens using both T. cruzi genes (asp-2 and ts) simultaneously and subsequently challenged with blood trypomastigotes. Immune responses before the challenge were confirmed by the presence of specific antibodies and peptide-specific T cells. Genetic vaccination did not confer protective immunity against acute infection with a lethal dose of the Colombian strain. in contrast, we observed a drastic reduction in parasitemia and a significant increase in survival, following challenge with an otherwise lethal dose of the Colombia strain. in many surviving animals with late-stage chronic infection, we observed alterations in the heart's electrical conductivity, compared to naive mice. in summary, we concluded that immunity against T cruzi antigens, similar to viruses and bacteria, may be strain-specific and have a negative impact on vaccine development. (c) 2009 Elsevier B.V. All rights reserved.