Impaired negative regulation of homeostatically proliferating T cells
Anna Shvets, Rabindranath Chakrabarti, Rosana Gonzalez-Quintial, Roberto Baccala, Argyrios N Theofilopoulos, Gérald J Prud'homme, Anna Shvets, Rabindranath Chakrabarti, Rosana Gonzalez-Quintial, Roberto Baccala, Argyrios N Theofilopoulos, Gérald J Prud'homme
Abstract
Acute lymphopenia-induced homeostatic proliferation (HP) of T cells promotes antitumor immunity, but the mechanism is unclear. We hypothesized that this is due to a lack of inhibitory signals that allows activation of T cells with low affinity for self-antigens. Tumors resist immunity in part by expressing inhibitory molecules such as PD-1 ligand 1 (PD-L1), B7-H4, and TGF-beta. In irradiated mice undergoing HP, we found that T cells displayed a severe deficit in the activation-induced expression of inhibitory molecules PD-1 and CTLA-4, and TGF-beta1-induced expression of Foxp3. HP T cells were also less suppressed by B7-H4/Ig and, unlike control T cells, failed to produce IL-10 in response to this molecule. This deficiency in regulation was reversed as normal T-cell numbers were restored. We conclude that T cells are weakly regulated by inhibitory molecules during the acute phase of HP, which could explain their increased effectiveness in cancer immunotherapy.
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Source: PubMed