Functional analysis of effector and regulatory T cells in a parasitic nematode infection.
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.
Rausch
Sebastian
S
Department of Molecular Parasitology, Humboldt-University Berlin, Philippstr. 13, 10115 Berlin, Germany.
Huehn
Jochen
J
Kirchhoff
Dennis
D
Rzepecka
Justyna
J
Schnoeller
Corinna
C
Pillai
Smitha
S
Loddenkemper
Christoph
C
Scheffold
Alexander
A
Hamann
Alf
A
Lucius
Richard
R
Hartmann
Susanne
S
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D023201:CD40 Ligand / Q000032:analysis; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D039001:Integrin alpha Chains / Q000032:analysis; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D015847:Interleukin-4 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009351:Nematospiroides dubius / Q000276:immunology* / Q000302:isolation & purification; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D017206:Strongylida Infections / Q000276:immunology* / Q000469:parasitology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000737:chemistry / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000737:chemistry / Q000276:immunology*
D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D039001:Integrin alpha Chains; D053645:Interleukin-2 Receptor alpha Subunit; C091367:alpha E integrins; D016753:Interleukin-10; D023201:CD40 Ligand; D015847:Interleukin-4