| Title: |
Long-lived CD4+IFN-γ+ T cells rather than short-lived CD4 + IFN-γ + IL-10 + T cells initiate rapid IL-10 production to suppress anamnestic T cell responses during secondary malaria infection |
| Authors: |
Villegas-Mendez, Ana; Inkson, Colette; Shaw, Tovah; Strangward, Patrick; Couper, Kevin |
| Source: |
Villegas-Mendez, A, Inkson, C, Shaw, T, Strangward, P & Couper, K 2016, 'Long-lived CD4+IFN-γ+ T cells rather than short-lived CD4 + IFN-γ + IL-10 + T cells initiate rapid IL-10 production to suppress anamnestic T cell responses during secondary malaria infection', Journal of Immunology, vol. 197, no. 8, pp. 3152-3164. https://doi.org/10.4049/jimmunol.1600968 |
| Publication Year: |
2016 |
| Collection: |
The University of Manchester: Research Explorer - Publications |
| Description: |
CD4 + T cells that produce IFN-γ are the source of host-protective IL-10 during primary infection with a number of different pathogens, including Plasmodium spp. The fate of these CD4 + IFN-γ + IL-10 + T cells following clearance of primary infection and their subsequent influence on the course of repeated infections is, however, presently unknown. In this study, utilizing IFN-γ–yellow fluorescent protein (YFP) and IL-10–GFP dual reporter mice, we show that primary malaria infection–induced CD4 + YFP + GFP + T cells have limited memory potential, do not stably express IL-10, and are disproportionately lost from the Ag-experienced CD4 + T cell memory population during the maintenance phase postinfection. CD4 + YFP + GFP + T cells generally exhibited a short-lived effector rather than effector memory T cell phenotype postinfection and expressed high levels of PD-1, Lag-3, and TIGIT, indicative of cellular exhaustion. Consistently, the surviving CD4 + YFP + GFP + T cell–derived cells were unresponsive and failed to proliferate during the early phase of secondary infection. In contrast, CD4 + YFP + GFP− T cell–derived cells expanded rapidly and upregulated IL-10 expression during secondary infection. Correspondingly, CD4 + T cells were the major producers within an accelerated and amplified IL-10 response during the early stage of secondary malaria infection. Notably, IL-10 exerted quantitatively stronger regulatory effects on innate and CD4 + T cell responses during primary and secondary infections, respectively. The results in this study significantly improve our understanding of the durability of IL-10–producing CD4 + T cells postinfection and provide information on how IL-10 may contribute to optimized parasite control and prevention of immune-mediated pathology during repeated malaria infections. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0022-1767; 1550-6606 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pissn/0022-1767; info:eu-repo/semantics/altIdentifier/eissn/1550-6606 |
| DOI: |
10.4049/jimmunol.1600968 |
| Availability: |
https://research.manchester.ac.uk/en/publications/1c5d1b2e-ddb0-47cf-8065-4d13b7988e54; https://doi.org/10.4049/jimmunol.1600968; https://www.scopus.com/pages/publications/84991458166 |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.DDBC9FEB |
| Database: |
BASE |