Abstract
The cell-to-cell contact of T lymphocytes with immunosuppressive macrophages causes marked changes in the tyrosine phosphorylation of some cytosolic proteins of T cells. By phosphoproteome analysis, we identified a 36-kDa protein as aldose reductase (AR). The AR expression in T cells was not changed by TCR stimulation or due to cell-to-cell transmission of suppressor signals from immunosuppressive macrophages. Therefore, AR phosphorylation/dephosphorylation is essential for the transduction of TCR-mediated T-cell stimulatory signals, and moreover plays important roles for the cross-talk of immunosuppressive macrophage-derived suppressor signals with the signaling pathways for T-cell activation. Moreover, AR played important roles in the upregulation of ERK1/2-mediated signaling pathways in T lymphocytes. Notably, the enzymatic activity of AR was not required for its signaling action. Taken together, it is concluded that AR mediates intracellular transmission of the suppressor signal of immunosuppressive macrophages toward downstream ERK1/2 pathways, possibly through its direct interaction with acceptor proteins.
Highlights
On Mycobacterium avium complex (MAC)-MΦ s, but not B7-2, ICAM-1, nor VCAM-1 molecule, plays important roles in the transmission of suppressor signals from MAC-MΦ s to target T cells through cell-to-cell interaction[13]
We previously observed that MAC-MΦ -derived suppressor signals are transmitted into target T cells via cell-to-cell contact and cause the dephosphorylation of Tyr residues of five cytosolic proteins with molecular weights (MWs) of around 35 kDa12
In the target T cells, intracellular expression of aldose reductase (AR) in protein levels was not altered in response to T cell receptor (TCR) stimulation or the transmission of suppressive signals from suppressor MΦ s via cell contact
Summary
On MAC-MΦ s, but not B7-2, ICAM-1, nor VCAM-1 molecule, plays important roles in the transmission of suppressor signals from MAC-MΦ s to target T cells through cell-to-cell interaction[13]. The mAb-blocking of CTLA-4 on target T cells did not reduce the suppressor activity of MAC-MΦ s, suggesting the role of a putative molecule on target T cells other than CTLA-4 as a receptor for B7-1LM of MAC-MΦ s13. In this context, the co-cultivation of T cells with MAC-MΦ s caused marked changes in the profiles of the tyrosine (Tyr) phosphorylation of several cytosolic proteins with molecular weights (MWs) of around 35 kDa12. We examined detailed profiles of the participation of AR in the intracellular transmission of immunosuppressive MΦ -derived suppressor signals in the target T cells
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