A novel gamma-delta T cell subset prevents malarial parasitemic recurrence
Abstract/Contents
- Abstract
- Malaria carries a heavy morbidity and mortality burden worldwide. Despite overwhelming evidence that gamma-delta T cells play an important role during malaria, the precise functional and phenotypic characteristics of these cells remain the least understood facets of the adaptive immune response during Plasmodium infection. We report that gamma-delta T cells were highly expanded and activated after the resolution of acute parasitemia in the Plasmodium chabaudi model of murine malaria, with a similarly activated gamma-delta T cell profile late after P. falciparum infection in human volunteers. Using single-cell paired-chain T cell receptor (TCR) sequencing, we determined that gamma-delta T cells were clonally expanded, were restricted to the TRAV15N-1 (Vdelta6.3) V-region, and had convergent complementarity-determining region 3 (CDR3) sequences, implying an antigen-specific gamma-delta T cell response. Whole trancriptome analysis of the expanded gamma-delta T cell population revealed an unexpected transcriptional profile that could promote recruitment and polarization of the myeloid compartment (Spp1 [osteopontin], Csf1 [M-CSF], Ccl3) -- suggesting a novel function for gamma-delta T cells. Never before shown in gamma-delta T cells, M-CSF protein was present in ~70% of the expanded gamma-delta T cells. Both gamma-delta T cells and M-CSF were found to be necessary for preventing parasitemic recrudescence following resolution of acute parasitemia. These findings indicate the presence of a novel subset of gamma-delta T cells that fill a specialized protective role in the late stage of malaria.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Mamedov, Murad R | |
|---|---|---|
| Associated with | Stanford University, Program in Immunology. | |
| Primary advisor | Davis, Mark | |
| Thesis advisor | Davis, Mark | |
| Thesis advisor | Boothroyd, John, 1948- | |
| Thesis advisor | Boyd, Scott, 1970- | |
| Thesis advisor | Chien, Yueh-Hsiu | |
| Thesis advisor | Schneider, David (David Samuel) | |
| Advisor | Boothroyd, John, 1948- | |
| Advisor | Boyd, Scott, 1970- | |
| Advisor | Chien, Yueh-Hsiu | |
| Advisor | Schneider, David (David Samuel) |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Murad R. Mamedov. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Murad Ramiz Mamedov
- License
- This work is licensed under a Creative Commons Attribution Non Commercial No Derivatives 3.0 Unported license (CC BY-NC-ND).
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