T-cell responsiveness of American cutaneous leishmaniasis patients to purified Leishmania pifanoi amastigote antigens and Leishmania braziliensis promastigote antigens: Immunologic patterns associated with cure

Sergio G. Coutinho, Marcia P. Oliveira, Alda M. Da-Cruz, Paula M. De Luca, Sergio C F Mendonça, Alvaro L. Bertho, Lynn Soong, Diane McMahon-Pratt

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Abstract

Patients suffering from American cutaneous leishmaniasis were studied before therapy (active lesion) and at the end of therapy (cured patients). Assays of lymphocyte proliferative responses of peripheral blood mononuclear cells induced in vitro by Leishmania braziliensis promastigote antigens (Lb) or by three proteins (A-2/P-2, P-4, and P-8) derived from Leishmania pifanoi amastigotes were performed. Antigen-stimulated cells were harvested for CD4 and CD8 phenotype analysis and the levels of gamma interferon (IFN-γ), interleukin 2 (IL-2) and interleukin 4 (IL-4) produced were also determined. Results show two different patterns of Lb-induced T cell responses: (a) predominance of responding CD4+ cells and mixed type 1 and type 2 cytokine production (IFN-γ, IL-2, and IL-4) during the active disease, (b) similar proportions of responding CD4+ and CD8+ cells and type 1 cytokine production (presence of IFN-γ and IL-2 and very low IL-4) at the end of therapy (healed lesions). Thus, this last pattern is probably associated with a beneficial T cell response. The A-2/P-2 amastigote cysteine proteinase provided only marginal (s.i. ≃ 2.5) T cell stimulation in 25% of patients studied: in contrast, the L. pifanoi P-4 and P-8 amastigote antigens induced significant stimulation (s.i. ≃ 5) in approximately 50% of the patients. In comparison to Lb-stimulated cultures, lower proliferative responses of T lymphocytes to P-4 or P-8 were observed. However, the P-4- or P-8-stimulated cultures had similar percentages of reactive CD4+ and CD8+ cells, as well as type 1 cytokines (presence of IFN-γ and IL-2, and low levels or absence of IL-4) in the supernatants both before and at the end of therapy. The consistent induction of apparently beneficial T cell responses by the P-4 and P-8 amastigote glycoproteins points to the possibility that these molecules be considered as candidates for future defined vaccines against leishmaniasis.

Original languageEnglish (US)
Pages (from-to)144-155
Number of pages12
JournalExperimental Parasitology
Volume84
Issue number2
DOIs
StatePublished - Nov 1996
Externally publishedYes

Fingerprint

Leishmania braziliensis
Cutaneous Leishmaniasis
Leishmania
Interleukin-4
Interleukin-2
T-Lymphocytes
Antigens
Interferons
Cytokines
Leishmaniasis Vaccines
Cysteine Proteases
Staphylococcal Protein A
Therapeutics
varespladib methyl
Interferon-gamma
Blood Cells
Glycoproteins
Lymphocytes
Phenotype

ASJC Scopus subject areas

  • Immunology
  • Parasitology
  • Infectious Diseases

Cite this

T-cell responsiveness of American cutaneous leishmaniasis patients to purified Leishmania pifanoi amastigote antigens and Leishmania braziliensis promastigote antigens : Immunologic patterns associated with cure. / Coutinho, Sergio G.; Oliveira, Marcia P.; Da-Cruz, Alda M.; De Luca, Paula M.; Mendonça, Sergio C F; Bertho, Alvaro L.; Soong, Lynn; McMahon-Pratt, Diane.

In: Experimental Parasitology, Vol. 84, No. 2, 11.1996, p. 144-155.

Research output: Contribution to journalArticle

Coutinho, Sergio G. ; Oliveira, Marcia P. ; Da-Cruz, Alda M. ; De Luca, Paula M. ; Mendonça, Sergio C F ; Bertho, Alvaro L. ; Soong, Lynn ; McMahon-Pratt, Diane. / T-cell responsiveness of American cutaneous leishmaniasis patients to purified Leishmania pifanoi amastigote antigens and Leishmania braziliensis promastigote antigens : Immunologic patterns associated with cure. In: Experimental Parasitology. 1996 ; Vol. 84, No. 2. pp. 144-155.
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abstract = "Patients suffering from American cutaneous leishmaniasis were studied before therapy (active lesion) and at the end of therapy (cured patients). Assays of lymphocyte proliferative responses of peripheral blood mononuclear cells induced in vitro by Leishmania braziliensis promastigote antigens (Lb) or by three proteins (A-2/P-2, P-4, and P-8) derived from Leishmania pifanoi amastigotes were performed. Antigen-stimulated cells were harvested for CD4 and CD8 phenotype analysis and the levels of gamma interferon (IFN-γ), interleukin 2 (IL-2) and interleukin 4 (IL-4) produced were also determined. Results show two different patterns of Lb-induced T cell responses: (a) predominance of responding CD4+ cells and mixed type 1 and type 2 cytokine production (IFN-γ, IL-2, and IL-4) during the active disease, (b) similar proportions of responding CD4+ and CD8+ cells and type 1 cytokine production (presence of IFN-γ and IL-2 and very low IL-4) at the end of therapy (healed lesions). Thus, this last pattern is probably associated with a beneficial T cell response. The A-2/P-2 amastigote cysteine proteinase provided only marginal (s.i. ≃ 2.5) T cell stimulation in 25{\%} of patients studied: in contrast, the L. pifanoi P-4 and P-8 amastigote antigens induced significant stimulation (s.i. ≃ 5) in approximately 50{\%} of the patients. In comparison to Lb-stimulated cultures, lower proliferative responses of T lymphocytes to P-4 or P-8 were observed. However, the P-4- or P-8-stimulated cultures had similar percentages of reactive CD4+ and CD8+ cells, as well as type 1 cytokines (presence of IFN-γ and IL-2, and low levels or absence of IL-4) in the supernatants both before and at the end of therapy. The consistent induction of apparently beneficial T cell responses by the P-4 and P-8 amastigote glycoproteins points to the possibility that these molecules be considered as candidates for future defined vaccines against leishmaniasis.",
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AU - Oliveira, Marcia P.

AU - Da-Cruz, Alda M.

AU - De Luca, Paula M.

AU - Mendonça, Sergio C F

AU - Bertho, Alvaro L.

AU - Soong, Lynn

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