Leishmania infantum induces expression of the negative regulatory checkpoint, CTLA-4, by human naïve CD8+ T cells.

Abstract

AIMS:

CD8+ T cells are important in mediating protective responses to intracellular pathogens. However, an uncontrolled response may lead to pathology. The role of CD8+ T cells in different clinical manifestations of human leishmaniasis is controversial and poorly understood. We aim to study the response of CD8+ T cells to the first exposure to different strains of Leishmania, seeking to correlate these findings with clinical manifestations of disease.

METHODS AND RESULTS:

We have evaluated the expression of granzyme A, inflammatory and anti-inflammatory cytokines, as well as CTLA-4 by human naïve CD8+ T cells exposed to Leishmania braziliensis and two different strains of Leishmania infantum in vitro. We observed that while exposure to L braziliensis induced an inflammatory profile, as measured by the expression of granzyme A, IFN-gamma and IL-17, as well as a higher IFN/IL-10 ratio, exposure to L infantum led to a regulatory profile, as measured by lower IFN/IL-10 ratio and higher expression of CTLA-4.

CONCLUSION:

These results may help explain why patients with the visceral clinical form present a weaker cellular response and, consequently, a worse outcome of the disease. The use of CTLA-4 checkpoint inhibitors may emerge as a potential immunotherapy to ameliorate the immune response in visceral leishmaniasis patients.

• Authors: Agostinho Gonçalves Viana, Luísa Mourão Dias Magalhães, Rodolfo Cordeiro Giunchetti, Walderez O Dutra, Kenneth J Gollob
• Journal: Parasite immunology (Parasite Immunol) Vol. 41 Issue 9 Pg. e12659 (09 2019) ISSN: 1365-3024 [Electronic] England
• PMID: 31173374 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 John Wiley & Sons Ltd.

Chemical References

• CTLA-4 Antigen
• CTLA4 protein, human
• Cytokines
• IL10 protein, human
• Interleukin-10
• Granzymes
• GZMA protein, human

Topics

• Adult
• CD8-Positive T-Lymphocytes (immunology)
• CTLA-4 Antigen (genetics)
• Cytokines (immunology)
• Female
• Granzymes (immunology)
• Humans
• Interleukin-10 (immunology)
• Leishmania braziliensis (physiology)
• Leishmania infantum (physiology)
• Leishmaniasis (immunology, parasitology)
• Leishmaniasis, Visceral (immunology)
• Male
• Principal Component Analysis