Article ; Online: ICOS signaling promotes a secondary humoral response after re-challenge with Plasmodium chabaudi chabaudi AS.
2020 Volume 16, Issue 4, Page(s) e1008527
Abstract: The co-stimulatory molecule ICOS is associated with the induction and regulation of T helper cell responses, including the differentiation of follicular helper T (Tfh) cells and the formation and maintenance of memory T cells. However, the role of ICOS ... ...
Abstract | The co-stimulatory molecule ICOS is associated with the induction and regulation of T helper cell responses, including the differentiation of follicular helper T (Tfh) cells and the formation and maintenance of memory T cells. However, the role of ICOS signaling in secondary immune responses is largely unexplored. Here we show that memory T cell formation and maintenance are influenced by persistent infection with P. chabaudi chabaudi AS infection, as memory T cell numbers decline in wild-type and Icos-/- mice after drug-clearance. Following drug-clearance Icos-/- mice display a relapsing parasitemia that occurs more frequently and with higher peaks compared to wild-type mice after re-challenge. The secondary immune response in Icos-/- mice is characterized by significant impairment in the expansion of effector cells with a Tfh-like phenotype, which is associated with a diminished and delayed parasite-specific Ab response and the absence of germinal centers. Similarly, the administration of an anti-ICOSL antagonizing antibody to wild-type mice before and after reinfection with P. c. chabaudi AS leads to an early defect in Tfh cell expansion and parasite-specific antibody production, confirming a need for ICOS-ICOSL interactions to promote memory B cell responses. Furthermore, adoptive transfer of central memory T (TCM) cells from wild-type and Icos-/- mice into tcrb-/- mice to directly evaluate the ability of TCM cells to give rise to Tfh cells revealed that TCM cells from wild-type mice acquire a mixed Th1- and Tfh-like phenotype after P. c. chabaudi AS infection. While TCM cells from Icos-/- mice expand and display markers of activation to a similar degree as their WT counterparts, they displayed a reduced capacity to upregulate markers indicative of a Tfh cell phenotype, resulting in a diminished humoral response. Together these findings verify that ICOS signaling in memory T cells plays an integral role in promoting T cell effector responses during secondary infection with P. c. chabaudi AS. |
---|---|
MeSH term(s) | Adoptive Transfer ; Animals ; B-Lymphocytes/immunology ; Cell Differentiation/immunology ; Germinal Center/immunology ; Immunity, Humoral/immunology ; Immunologic Memory ; Inducible T-Cell Co-Stimulator Protein/immunology ; Inducible T-Cell Co-Stimulator Protein/metabolism ; Lymphocyte Activation/immunology ; Malaria/immunology ; Malaria/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Plasmodium chabaudi/metabolism ; Plasmodium chabaudi/pathogenicity ; Signal Transduction ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism |
Chemical Substances | ICOS protein, human ; Icos protein, mouse ; Inducible T-Cell Co-Stimulator Protein |
Language | English |
Publishing date | 2020-04-29 |
Publishing country | United States |
Document type | Journal Article ; Research Support, N.I.H., Extramural |
ZDB-ID | 2205412-1 |
ISSN | 1553-7374 ; 1553-7374 |
ISSN (online) | 1553-7374 |
ISSN | 1553-7374 |
DOI | 10.1371/journal.ppat.1008527 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.