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Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.
Published on: September 1, 2015
B7-1-dependent co-stimulation results in qualitatively and quantitatively different responses by CD4+ and CD8+ T
1The Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455, USA.
Insights
Native B7-1 co-stimulation is sufficient for T cell effector function but not sustained CD8+ responses. Higher B7-1 density is needed for CD8+ T cell activation compared to CD4+ T cells.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Biology
Background:
- T cell activation requires co-stimulatory signals in addition to antigen recognition.
- B7-1 is a key co-stimulatory molecule involved in T cell immune responses.
- Understanding B7-1's precise role necessitates isolating its effects from other interactions.
Purpose of the Study:
- To investigate the co-stimulatory capacity of purified native B7-1.
- To determine if B7-1 alone can induce T cell activation and effector function.
- To compare the dose-dependent effects of B7-1 on CD4+ and CD8+ T cell responses.
Main Methods:
- Purification of native B7-1 using monoclonal antibody affinity chromatography.
- Immobilization of purified B7-1 on latex microspheres with anti-T cell receptor (TCR) antibody.
- Assessment of T cell proliferation, effector function, motility, and adhesion.
Main Results:
- Immobilized B7-1 effectively stimulated both CD4+ and CD8+ T cell activation, proliferation, and effector function.
- CD4+ T cell responses were prolonged, with significant interleukin-2 production and clonal expansion.
- CD8+ T cell responses were transient, peaking around days 3-4, followed by cell death, indicating insufficient sustained co-stimulation for helper-independent responses.
- CD8+ T cells required higher B7-1 densities for activation compared to CD4+ T cells.
- Purified B7-1 did not co-stimulate when presented separately from the TCR stimulus, unlike B7-1 transfectants.
Conclusions:
- B7-1 mediated co-stimulation is sufficient for inducing effector function in both CD4+ and CD8+ T cell precursors.
- B7-1 co-stimulation alone is insufficient for sustaining helper-independent CD8+ cytotoxic T lymphocyte (CTL) responses.
- The density of B7-1 expressed by antigen-presenting cells (APCs) may influence the balance between helper T cell and CTL responses.
Abstract:
To characterize better the co-stimulatory activity of native B7-1 in the absence of other receptor/ligand interactions that might contribute to the response, B7-1 was purified by monoclonal antibody (mAb) affinity chromatography. Immobilization of purified B7-1 with anti-T cell receptor (TCR) mAb on cell-sized latex microspheres provided an effective stimulus for activation of both CD4+ and CD8+ T cells as measured by proliferation, development of effector function, and changes in motility and adhesion. The CD4+ T cell response was prolonged and resulted in efficient interleukin-2 production and clonal expansion. In contrast, CD8+ responses were transient. Proliferation and clonal expansion peaked on days 3 and 4, coincident with maximal expression of lytic effector function, and the cells then died. These results demonstrate that B7-1 mediated co-stimulation is sufficient for the induction of effector function in both helper and cytotoxic T cell precursors, but suggest that B7-1 co-stimulation is not sufficient to sustain helper-independent CD8+ CTL responses. When the dose responses of CD4+ and CD8+ T cells to B7-1 were compared, CD8+ T cells were found to require higher densities of B7-1 to attain an equivalent level of activation, suggesting that the level of expression of B7-1 by APC may influence the development of helper or CTL responses. Finally, in contrast to results obtained by others with B7-1 transfectants, purified B7-1 did not provide co-stimulation when presented on a surface separate from the TCR stimulus.
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