CD25+ T cells induce Helicobacter pylori-specific CD25- T-cell anergy but are not required to maintain persistent hyporesponsiveness.
The gastric pathogen Helicobacter pylori infects over half the world's population. The lifelong infection induces gastric inflammation but the host fails to generate protective immunity. To study the lack of protective H. pylori immunity, CD4(+)CD25(+) T(reg) cells were investigated for their ability to down-regulate H. pylori-specific CD4(+)CD25(-) cells in a murine model. CD25(-) lymphocytes from infected mice were hyporesponsive to antigenic stimulation in vitro even in the absence of CD25(+) T(reg) cells unless treated with high-dose IL-2. Transfer of CD45RB(hi) naïve CD25(-) cells from infected mice into rag1(-/-) mice challenged with H. pylori resulted in severe gastritis and reduced bacterial loads, whereas transfer of CD45RB(lo) memory CD25(-) cells from H. pylori-infected mice resulted in only mild gastritis and persistent infection. CD25(-) cells stimulated in the absence of CD25(+) cells in rag1(-/-) mice promoted bacterial clearance, but lost this ability when subsequently transferred to WT mice harboring CD25(+) cells. These results demonstrate that CD25(+) cells induce anergy in CD25(-) cells in response to H. pylori infection but are not required to maintain hyporesponsiveness. In addition, CD25(+) cells are able to suppress previously activated CD25(-) cells when responding to H. pylori challenge in vivo.
Stuller
Kathleen A
KA
Nationwide Children's Research Institute, Columbus, OH, USA.
Ding
Hua
H
Redline
Raymond W
RW
Czinn
Steven J
SJ
Blanchard
Thomas G
TG
D000818:Animals; D018959:CD57 Antigens; D017635:Clonal Anergy / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005756:Gastritis / Q000276:immunology / Q000382:microbiology; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D018959:CD57 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit