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Lipopolysaccharide-Activated CD4⁺CD25⁺ T Regulatory Cells Inhibit Neutrophil Function and Promote Their Apoptosis and Death¹

Przemysaw Lewkowicz^2,*, Natalia Lewkowicz, Andrzej Sasiak^* and Henryk Tchórzewski^*

^* Department of Clinical Immunology, Institute of Polish Mother’s Hospital, Lodz, Poland; and Department of Periodontal and Oral Mucosal Diseases, Medical University of Lodz, Poland

CD4⁺CD25⁺ T regulatory (Treg) cells play a central role in the suppression of immune response and prevention of autoimmune reactions. Pathogen recognition receptors expressed by immune cells, such as TLRs, may provide a critical link between the innate and adaptive immune systems. There is also evidence that TLR ligands can directly modulate the suppressive capacity of Treg cells. Here, we showed that CD4⁺CD25⁺ Treg cells affect neutrophil function and survival and that the TLR4 ligand is involved in the regulation of the cell interactions. We found that LPS-activated Treg cells inhibit reactive oxygen intermediates and cytokine production by neutrophils. Moreover, Treg cells reverse LPS-induced survival of neutrophils and promote their apoptosis and death. We also found that TCR-activated Treg cells induce the same effects on polymorphonuclear neutrophils as those achieved by TLR4 stimulation. Importantly, the suppressive potential of CD4⁺CD25⁺ Treg cells induced by LPS seems to be partially IL-10 and TGF-β dependent, whereas anti-CD3/CD28 stimulation is rather contact dependent. Together, these observations suggest that Treg cells have the ability to directly regulate neutrophil function and life span when both types of the cells are exposed to LPS.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by State Committee for Scientific Research of Poland Grants KBN 3 P05A 06725 and KBN 2 P05E 09126.

² Address correspondence and reprint requests to Dr. Przemysaw Lewkowicz, Department of Clinical Immunology, Institute of Polish Mother’s Hospital, Rzgowska Street 281/289, 93-338 Lodz, Poland. E-mail address: natalewk{at}wp.pl

³ Abbreviations used in this paper: PMN, polymorphonuclear neutrophil; ANXV, annexin V; CBA, cytometric bead array; FSC, forward scatter; PI, propidium iodide; ROI, reactive oxygen intermediate; SSC, side scatter; Treg, T regulatory.

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