Sialophorin is necessary for vaccine-induced CD8+ T cell responses and immunity against lethal fungal pneumonia in CD4+ T-cell deficient hosts
| Autor: | Srinivasu Mudalagiriyappa, Som G. Nanjappa |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 206:16.06-16.06 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Increased opportunistic fungal infections in immunocompromised patients and lack of effective therapeutic modalities caused millions of deaths worldwide. Further, there are no licensed vaccines available for such and for immune-sufficient individuals. Previously, we have shown that in the absence of CD4+ T cells, vaccine-induced CD8+ T cells can mount sterilizing fungal immunity. However, molecules that have an immunomodulatory effect on CD8+ T cells are still to be explored. Using a mouse model of CD4+ T cell lymphopenia and experimental fungal vaccine, we demonstrate that Sialophorin (CD43), a molecule deficient in WAS patients, plays a critical role in mounting anti-fungal immunity. Genetic ablation of CD43 resulted in blunted CD8+ T cell responses associated with reduced expression of prototypic lineage-specific transcription factors following vaccination. Cell-intrinsic expression of CD43 on CD8+ T cells was indispensable for their expansion. Poor vaccine-induced effector CD8+ T cell responses under CD43-deficiency caused the failure to control fungal pneumonia following lethal challenge, independent of trafficking defect of the CD43-deficient effector cells. Further, we demonstrate antigen-specific CD8+ T cells preferentially expressed glycosylated-CD43. Notably, the numbers of glycosylated-CD43+ CD8+ T cells were directly correlated with vaccine-immunity. Thus, the glycosylated-CD43 expression on the CD8+ T cells could serve as a biological marker of vaccine efficacy and clinical outcome of fungal pneumonia. In conclusion, we report that CD43 is required for effective vaccine-immunity against lethal fungal pneumonia, and glycosylated-CD43 could be a novel phenotypic T-cell marker of fungal immunity. |
| Databáze: | OpenAIRE |
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