CD8 T Cell Exhaustion in Human Visceral Leishmaniasis

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2013 Aug 8

PMID 23922369

Citations 70

Authors

Shalini Gautam

Rajiv Kumar

Neetu Singh

Abhishek Kumar Singh

Madhukar Rai

David Sacks

Shyam Sundar

Susanne Nylen

Affiliations

Soon will be listed here.

Abstract

Little is known about CD8 T cells in human visceral leishmaniasis (VL) and it is unclear if these cells have a protective, pathological and/or suppressive function. In experimental VL CD8 T cells have been shown to contribute to parasite control and play an important role in vaccine-generated immunity. To better understand the role of CD8 T cells in human VL, we examined molecules associated with anergy and cytotoxic T lymphocytes (CTL) in peripheral blood mononuclear cells (PBMC) and splenic aspirates (SA), and in CD8 cells derived from these tissues. Gene and surface marker expression suggest that splenic CD8 cell predominantly display an anergic phenotype, whereas CD8-PBMC have features of both anergic cells and CTLs. CD8 cells contribute to the baseline IFNγ levels in whole blood (WB) and SA cultures, but not to the Leishmania induced IFNγ release that is revealed using WB cultures. Blockade of CTLA-4 or PD1 had no effect on IFNγ production or parasite survival in SA cultures. Following cure, CD8 T cells contribute to the Leishmania induced IFNγ production observed in Leishmania stimulated cell cultures. We suggest CD8 T cells are driven to anergy/exhaustion in human VL, which affect their ability to contribute to protective immune responses.

Citing Articles

The development and maintenance of immunity against visceral leishmaniasis.

Tiwari R, Kumar A, Singh V, Rajneesh , Bhushan Chauhan S, Sundar S Front Immunol. 2025; 15:1486407.

PMID: 39781380 PMC: 11707418. DOI: 10.3389/fimmu.2024.1486407.

Chemokines Signature and T Cell Dynamics in Leishmaniasis: Molecular insight and therapeutic application.

Upadhyay S, Kumar S, Singh V, Tiwari R, Kumar A, Sundar S Expert Rev Mol Med. 2024; 1-55.

PMID: 39587036 PMC: 11707835. DOI: 10.1017/erm.2024.36.

T-cell and Soluble Co-inhibitory Receptor Expression in Patients With Visceral Leishmaniasis Are Markers of Treatment Response and Clinical Outcome.

Ademe M, Osorio Y, Fikre H, Adane D, Mulaw T, Travi B Open Forum Infect Dis. 2024; 11(11):ofae649.

PMID: 39564149 PMC: 11574617. DOI: 10.1093/ofid/ofae649.

Low Plasma Lipids Are Associated with Relapsing and Lethal Visceral Leishmaniasis in HIV-Infected Patients.

Silva R, Uliana S, Yasunaka J, Veloso C, Sousa E, Ferreira M Pathogens. 2024; 13(6).

PMID: 38921748 PMC: 11206293. DOI: 10.3390/pathogens13060450.

Persistent T cell unresponsiveness associated with chronic visceral leishmaniasis in HIV-coinfected patients.

de Vrij N, Pollmann J, Rezende A, Ibarra-Meneses A, Pham T, Hailemichael W Commun Biol. 2024; 7(1):524.

PMID: 38702419 PMC: 11068874. DOI: 10.1038/s42003-024-06225-2.

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