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Functional Analysis of Effector and Regulatory T Cells in a Parasitic Nematode Infection

Department of Molecular Parasitology, Humboldt-University, Berlin 10115, Germany,¹ Experimental Rheumatology, Charité Berlin, Berlin 10117, Germany,² Immunomodulation Group, Deutsches Rheuma-Forschungszentrum Berlin, Berlin 10117, Germany,³ Pathology/RCIS, Charité Berlin, Berlin 12200, Germany⁴

Received 7 September 2007/ Returned for modification 10 October 2007/ Accepted 15 February 2008

Parasitic nematodes typically modulate T-cell reactivity, primarily during the chronic phase of infection. We analyzed the role of CD4-positive (CD4⁺) T effector (T_eff) cells and regulatory T (T_reg) cells derived from mice chronically infected with the intestinal nematode Heligmosomoides polygyrus. Different CD4⁺ T-cell subsets were transferred into naïve recipients that were subsequently infected with H. polygyrus. Adoptive transfer of conventional T_eff cells conferred protection and led to a significant decrease in the worm burdens of H. polygyrus-infected recipients. Roughly 0.2% of the CD4⁺ T cells were H. polygyrus specific based on expression of CD154, and cells producing interleukin 4 (IL-4) and IL-13 were highly enriched within the CD154⁺ population. In contrast, adoptive transfer of T_reg cells, characterized by the markers CD25 and CD103 and the transcription factor Foxp3, had no effect on the worm burdens of recipients. Further analysis showed that soon after infection, the number of Foxp3⁺ T_reg cells temporarily increased in the inflamed tissue while effector/memory-like CD103⁺ Foxp⁺ T_reg cells systemically increased in the draining lymph nodes and spleen. In addition, T_reg cells represented a potential source of IL-10 and reduced the expression of IL-4. Finally, under in vitro conditions, T_reg cells from infected mice were more potent suppressors than cells derived from naïve mice. In conclusion, our data indicate that small numbers of T_eff cells have the ability to promote host protective immune responses, even in the presence of T_reg cells.

Published ahead of print on 3 March 2008.

Editor: J. F. Urban, Jr.