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Updated: May 31, 2026
Retroviral Transduction of Bone Marrow Progenitor Cells to Generate T-cell Receptor Retrogenic Mice
Published on: July 11, 2016
A TCR transgenic mouse reactive with multiple systemic dimorphic fungi
Marcel Wüthrich1, Chiung Yu Hung, Ben H Gern
1Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792, USA. mwuethri@wisc.edu
Abstract:
Dimorphic fungi collectively account for 5-10 million new infections annually worldwide. Ongoing efforts seek to clarify mechanisms of cellular resistance to these agents and develop vaccines. A major limitation in studying the development of protective T cells in this group of organisms is the lack of tools to detect, enumerate, and characterize fungus-specific T cells during vaccination and infection. We generated a TCR transgenic mouse (Bd 1807) whose CD4(+) T cells respond to a native epitope in Blastomyces dermatitidis and also in Histoplasma capsulatum. In this study, we characterize the mouse, reveal its applications, and extend our analysis showing that 1807 cells also respond to the related dimorphic fungi Coccidioides posadasii and Paracoccidioides lutzii. On adoptive transfer into vaccinated wild-type mice, 1807 cells become activated, proliferate, and expand in the draining lymph nodes, and they differentiate into T1 effectors after trafficking to the lung upon lethal experimental challenge. Bd 1807 cells confer vaccine-induced resistance against B. dermatitidis, H. capsulatum, and C. posadasii. Transfer of naive 1807 cells at serial intervals postvaccination uncovered the prolonged duration of fungal Ag presentation. Using 1807 cells, we also found that the administration of vaccine only once induced a maximal pool of effector/memory CD4(+) cells and protective immunity by 4 wk after vaccination. The autologous adoptive transfer system described in this study reveals novel features of antifungal immunity and offers a powerful approach to study the differentiation of Ag-specific T cells responsive to multiple dimorphic fungi and the development of CD4(+) T cell memory needed to protect against fungal infection.
Insights
Researchers developed a new mouse model to study T cell responses against fungal infections. This tool aids in understanding antifungal immunity and developing effective vaccines against dimorphic fungi.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Dimorphic fungi cause millions of infections annually, necessitating better understanding of host resistance mechanisms.
- Current research faces limitations in tools for studying fungus-specific T cell responses during vaccination and infection.
- Developing effective vaccines against these fungi requires detailed knowledge of cellular immunity.
Purpose of the Study:
- To characterize a novel TCR transgenic mouse model (Bd 1807) for studying T cell responses to dimorphic fungi.
- To evaluate the utility of this model in assessing antifungal immunity and vaccine efficacy.
- To investigate the duration of antigen presentation and CD4+ T cell memory development.
Main Methods:
- Generation of a TCR transgenic mouse (Bd 1807) with CD4+ T cells reactive to dimorphic fungi.
- Adoptive transfer of 1807 cells into vaccinated wild-type mice.
- Analysis of T cell activation, proliferation, differentiation, and trafficking following fungal challenge.
- Assessment of vaccine-induced resistance conferred by 1807 cells.
Main Results:
- The Bd 1807 mouse model's CD4+ T cells respond to Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides posadasii, and Paracoccidioides lutzii.
- Adoptively transferred 1807 cells differentiate into T1 effectors and confer vaccine-induced resistance against multiple fungal species.
- The study revealed prolonged fungal antigen presentation and maximal effector/memory CD4+ T cell pool by 4 weeks post-vaccination.
Conclusions:
- The Bd 1807 mouse model provides a powerful tool for studying antifungal immunity and T cell differentiation against multiple dimorphic fungi.
- This model facilitates research into CD4+ T cell memory development crucial for protection against fungal infections.
- The findings offer novel insights into antifungal immune responses and vaccine strategies.
