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. |
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| 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 |
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