Milken Institute School of Public Health Poster Presentations (Marvin Center & Video)

Title

Role of Il-21 in CD8 T cell response against E.cuniculi infection

Poster Number

55

Document Type

Poster

Status

Graduate Student - Masters

Abstract Category

Epidemiology and Biostatistics

Keywords

microsporidia, CD8 T cells, CD4 T cells, IL-21, cytotoxicity

Publication Date

4-2017

Abstract

Microsporidia are a group of obligate intracellular opportunistic parasites that induce a wide-range of pathology in immunocompromised individuals, including HIV-AIDS patients, organ transplant recipients, cancer patients and the elderly. Among the many species of microsporidia, at least eight can infect humans, but the pathogen is often underdiagnosed due to its small size and the need to be identified by specialized staining techniques. Encephalitozoon cuniculi is a microsporidia with one of the widest host ranges among mammals and has the ability to disseminate into multiple tissues. Due to the fact that it can be cultured in the laboratory, a majority of experimental studies have been conducted with E.cuniculi.

In a mouse model of E.cuniculi infection, robust CD8 T cell response manifested by strong polyfunctional characteristics (both IFNg and cytolytic activity) is critical for host protection. Interestingly, the parasite does not induce a high inflammatory environment, and the CD8 T cell response elicited after oral/natural infection is independent of IL-2 and primarily driven by IL-21. Although importance of IL-21 is associated with B cell responses, this cytokine has also been reported to play a critical role in maintaining a robust CD8 T cell memory. We observed that in the absence of IL-21 signaling (IL-21R KO), effector CD8 T cell response to E.cuniculi infection was reduced both in terms of number and polyfunctionality. T follicular helper cells (TFH) are considered to be the major source of IL-21 and this CD4 T cell subset is critical for the formation of germinal centers, which is dependent on signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) expression.

SAP knock out animals were used to study the role of this CD4 T cell subset in programing of effector CD8 T cell response against E.cuniculi. Intracellular staining analysis showed that TFH (ICOShiPD1hi CD4 T cells) are the main producers of IL-21 during early infection. As compared to wild type animals, SAP-/- mice exhibited lower IL-21 production at day 5-post infection. Interestingly, although the knock out mice exhibited increased short-lived effector CD8 T cell response (SLEC; KLRG1+CD127-) in terms of numbers, their polyfunctionality (IFNg production and significantly impaired cytotoxicity) was reduced. Moreover, activation status of SAP deficient SLECs (based on CD43 staining), in comparison to cells from wild type mice was also decreased. These findings strongly suggest that early IL-21 production by TFH may be critical for optimal effector CD8 T cell immunity against E.cuniculi infection.

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

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Comments

To be presented at GW Annual Research Days 2017.

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Role of Il-21 in CD8 T cell response against E.cuniculi infection

Microsporidia are a group of obligate intracellular opportunistic parasites that induce a wide-range of pathology in immunocompromised individuals, including HIV-AIDS patients, organ transplant recipients, cancer patients and the elderly. Among the many species of microsporidia, at least eight can infect humans, but the pathogen is often underdiagnosed due to its small size and the need to be identified by specialized staining techniques. Encephalitozoon cuniculi is a microsporidia with one of the widest host ranges among mammals and has the ability to disseminate into multiple tissues. Due to the fact that it can be cultured in the laboratory, a majority of experimental studies have been conducted with E.cuniculi.

In a mouse model of E.cuniculi infection, robust CD8 T cell response manifested by strong polyfunctional characteristics (both IFNg and cytolytic activity) is critical for host protection. Interestingly, the parasite does not induce a high inflammatory environment, and the CD8 T cell response elicited after oral/natural infection is independent of IL-2 and primarily driven by IL-21. Although importance of IL-21 is associated with B cell responses, this cytokine has also been reported to play a critical role in maintaining a robust CD8 T cell memory. We observed that in the absence of IL-21 signaling (IL-21R KO), effector CD8 T cell response to E.cuniculi infection was reduced both in terms of number and polyfunctionality. T follicular helper cells (TFH) are considered to be the major source of IL-21 and this CD4 T cell subset is critical for the formation of germinal centers, which is dependent on signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) expression.

SAP knock out animals were used to study the role of this CD4 T cell subset in programing of effector CD8 T cell response against E.cuniculi. Intracellular staining analysis showed that TFH (ICOShiPD1hi CD4 T cells) are the main producers of IL-21 during early infection. As compared to wild type animals, SAP-/- mice exhibited lower IL-21 production at day 5-post infection. Interestingly, although the knock out mice exhibited increased short-lived effector CD8 T cell response (SLEC; KLRG1+CD127-) in terms of numbers, their polyfunctionality (IFNg production and significantly impaired cytotoxicity) was reduced. Moreover, activation status of SAP deficient SLECs (based on CD43 staining), in comparison to cells from wild type mice was also decreased. These findings strongly suggest that early IL-21 production by TFH may be critical for optimal effector CD8 T cell immunity against E.cuniculi infection.