Macrophages as stimulators of MART-1 27-35 epitope-specific human cytolytic T lymphocytes in vitro
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Shikhar Mehrotra1, Nisar Zaidi, Nitya G Chakraborty
1Department of Medicine, University of Connecticut School of Medicine, Farmington, CT, USA. mehrotr@musc.edu
Background:
Activation and expansion of antigen-specific cytolytic T lymphocytes (CTL) require epitope presented by antigen-presenting cells (APC). Presently, dendritic cells (DC) are viewed as the most efficient APC. Since the recognition of DCs as the professional APC, the paradigm has emerged that macrophage (MPhi) are scavengers and are incapable of activating T cells.
Method:
The melanoma-associated MART-1(27-35) peptide-loaded MPhi from HLA-A2-positive donors were used to activate MART-1(27-35) epitope-specific CTL in vitro.
Results:
We show that peptide-pulsed MPhi stimulate MART-1(27-35) epitope-specific precursors to proliferate and to express effector functions. We also show that upon restimulation with the peptide pulsed MPhi, a fraction of the epitope-specific CTLs undergoes activation-induced cell death. The activation-induced cell death is induced in an epitope-specific manner and through apoptosis.
Conclusion:
MPhi can function as APC and are also capable of modulating expansion and contraction of CTL response in vitro.
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