Multifunctional CD4⁺ T cells in patients with American cutaneous leishmaniasis

A B B Macedo1, J C Sánchez-Arcila, A O Schubach

  • 1Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.

Insights

Investigating T helper type 1 (Th1) responses in leishmaniasis patients revealed that Leishmania braziliensis antigens induce more multifunctional T cells than Leishmania amazonensis antigens. This difference in T cell quality may explain susceptibility to L. amazonensis infection.

Area of Science:

  • Immunology
  • Parasitology
  • Infectious Diseases

Background:

  • Leishmaniasis affects millions globally, necessitating a deeper understanding of immune responses.
  • T helper type 1 (Th1) cells are crucial in controlling parasitic infections like leishmaniasis.
  • Assessing the quality, not just quantity, of Th1 responses is vital for understanding disease pathogenesis.

Purpose of the Study:

  • To compare the quality of T helper type 1 (Th1) responses induced by Leishmania braziliensis (LbAg) and Leishmania amazonensis (LaAg) antigens.
  • To evaluate the induction of multifunctional CD4(+) T cells in healed cutaneous leishmaniasis patients.
  • To correlate Th1 response quality with susceptibility to Leishmania infection.

Main Methods:

  • Application of multiparametric flow cytometry on peripheral blood mononuclear cells from healed cutaneous leishmaniasis patients.
  • Stimulation of cells with crude antigen extracts from L. braziliensis (LbAg) and L. amazonensis (LaAg) promastigotes.
  • Analysis of interferon-gamma (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α) production by CD4(+) T cells.

Main Results:

  • No significant difference in total IFN-γ-producing CD4(+) T cells between LbAg and LaAg.
  • LbAg induced a higher proportion of multifunctional Th1 cells (28%) compared to LaAg (predominantly single-positive cells, 68%).
  • Multifunctional Th1 cells stimulated by LbAg exhibited significantly higher MFI for IFN-γ and IL-2 than those stimulated by LaAg.

Conclusions:

  • The quality of Th1 response, specifically the generation of multifunctional CD4(+) T cells, differs significantly between LbAg and LaAg.
  • The lower induction of multifunctional Th1 cells by LaAg may contribute to the high susceptibility observed in L. amazonensis-infected individuals.
  • Evaluating the quality of Th1 responses is crucial for understanding the immunopathogenesis of American tegumentary leishmaniasis.

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