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https://www.arca.fiocruz.br/handle/icict/7442
FLOW CYTOMETRIC DETERMINATION OF CELLULAR SOURCES AND FREQUENCIES OF KEY CYTOKINE-PRODUCING LYMPHOCYTES DIRECTED AGAINST RECOMBINANT LACK
Citocinas/biossíntese
Citometria de Fluxo
Leishmaniose Cutânea/imunologia
Proteínas de Protozoários/imunologia
Humanos
Células Th1/imunologia
Interferon gama/biossíntese
Interleucina-10/biossíntese
Proteínas Recombinantes/imunologia
Fator de Necrose Tumoral alfa/biossíntese
Author
Affilliation
Universidade Federal de Minas Gerais. Department of Biochemistry-Immunology. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Medical Center. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Department of Morphology. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Medical Center. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Department of Biochemistry-Immunology. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Medical Center. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Medical Center. Belo Horizonte, MG, Brasil
Universidade Federal da Bahia. Medical Center. Salvador, BA, Brasil
Universidade Federal da Bahia. Medical Center. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Universidade Federal da Bahia. Medical Center. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Universidade Federal da Bahia. Medical Center. Salvador, BA, Brasil
Universidade Federal de Minas Gerais. Department of Parasitology. Belo Horizonte, MG, Brasil
UCSF Medical Center. San Francisco, California
Universidade Federal de Minas Gerais. Department of Biochemistry-Immunology. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Department of Morphology. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Medical Center. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Department of Biochemistry-Immunology. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Medical Center. Belo Horizonte, MG, Brasil
Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Medical Center. Belo Horizonte, MG, Brasil
Universidade Federal da Bahia. Medical Center. Salvador, BA, Brasil
Universidade Federal da Bahia. Medical Center. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Universidade Federal da Bahia. Medical Center. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil
Universidade Federal da Bahia. Medical Center. Salvador, BA, Brasil
Universidade Federal de Minas Gerais. Department of Parasitology. Belo Horizonte, MG, Brasil
UCSF Medical Center. San Francisco, California
Universidade Federal de Minas Gerais. Department of Biochemistry-Immunology. Belo Horizonte, MG, Brasil
Abstract
Leishmaniasis, caused by infection with the protozoan parasite Leishmania, affects millions of individuals
worldwide, causing serious morbidity and mortality. This study directly determined the frequency of cells
producing key immunoregulatory cytokines in response to the recombinant antigen Leishmania homolog of
receptors for activated kinase C (LACK) and soluble leishmania antigen (SLA), and it determined relative
contributions of these antigens to the overall cytokine profile in individuals infected for the first time with
Leishmania braziliensis. All individuals presented with the cutaneous clinical form of leishmaniasis and were
analyzed for proliferative responses to LACK antigen and SLA, frequency of lymphocyte subpopulations
(analyzed ex vivo), and antigen-induced (LACK and SLA) cytokine production at the single-cell level (determined
by flow cytometry). The following were determined. (i) The Th1-type response previously seen in patients
with cutaneous leishmaniasis is due to gamma interferon (IFN-g) production by several different sources,
listed in order of contribution: CD41 T lymphocytes, CD42, CD82 lymphocytes, and CD81 T lymphocytes. (ii)
SLA induced a higher frequency of lymphocytes producing IFN-g and tumor necrosis factor alpha (TNF-a)
than did LACK. (iii) LACK induced an activation of monocyte populations as reflected by an increased
percentage of CD14-positive cells. (iv) Neither SLA nor LACK induced detectable frequencies of cells producing
interleukin-4 (IL-4) or IL-5. These data demonstrated a multifaceted immune response to SLA in human
leishmaniasis involving Th1 CD41 T lymphocytes (IFN-g1 and IL-102/IL-42), Tc1 CD81 T cells (IFN-g1, and
IL-102/IL-42), and a high frequency of TNF-a-producing lymphocytes. Moreover, it was determined that the
recombinant antigen LACK acts as a weak inducer of Th1-type lymphocyte responses compared to SLA.
DeCS
Antígenos de Protozoários/imunologiaCitocinas/biossíntese
Citometria de Fluxo
Leishmaniose Cutânea/imunologia
Proteínas de Protozoários/imunologia
Humanos
Células Th1/imunologia
Interferon gama/biossíntese
Interleucina-10/biossíntese
Proteínas Recombinantes/imunologia
Fator de Necrose Tumoral alfa/biossíntese
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