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Direct physical interaction involving CD40 ligand on T cells and CD40 on B cells is required to propagate MMTV
A V Chervonsky1, J Xu, A K Barlow
1Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, Connecticut 06510, USA.
Abstract:
The propagation of mouse mammary tumor virus (MMTV) has been analyzed in mice defective for expression of CD40 ligand (CD40L). Mice with endogenous viral superantigen (SAG) delete T cells with cognate V beta independent of CD40L expression. Nevertheless, CD40L-mice do not show deletion of cognate T cells after being exposed to infectious MMTV and have greatly diminished viral replication. The response of CD40L- T cells to SAG in vitro is also impaired, but can be reconstituted by adding B cells activated by recombinant CD40L to express costimulatory molecules. Thus, direct CD40L-dependent B cell activation appears to be a critical step in the life cycle of MMTV. The initial step in SAG-dependent T cell activation, and hence the MMTV life cycle, may be mediated by non-B cells, because splenocytes from B cell-deficient SAG-transgenic mice are able to activate cognate T cells.
Insights
CD40 ligand (CD40L) is crucial for mouse mammary tumor virus (MMTV) replication. Its absence impairs viral spread and T cell responses, highlighting CD40L-dependent B cell activation as vital for MMTV propagation.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Mouse mammary tumor virus (MMTV) propagation relies on host immune responses.
- CD40 ligand (CD40L) plays a role in T cell activation and immune regulation.
- Viral superantigens (SAGs) can induce T cell deletion.
Purpose of the Study:
- To investigate the role of CD40L in MMTV propagation and T cell responses.
- To determine the impact of CD40L deficiency on MMTV replication and viral superantigen (SAG)-mediated T cell deletion.
Main Methods:
- Analysis of MMTV propagation in CD40L-deficient mice.
- Assessment of T cell deletion in response to SAG in CD40L-deficient mice.
- In vitro studies of T cell responses to SAG with and without B cells.
Main Results:
- CD40L-deficient mice exhibit diminished MMTV replication and impaired T cell deletion upon MMTV exposure.
- T cell responses to SAG in vitro are impaired in the absence of CD40L.
- B cells activated by CD40L can restore T cell responses to SAG.
Conclusions:
- CD40L-dependent B cell activation is critical for MMTV propagation.
- CD40L signaling is essential for effective T cell responses to MMTV and SAG.
- Non-B cells may initiate SAG-dependent T cell activation in the early stages of MMTV infection.