CD4+CD25+ regulatory T cells in the small intestinal lamina propria show an effector/memory phenotype.
CD4(+)CD25(+) regulatory T cells (Tregs) have been implicated in the suppression of pathogenic responses to both self- and non-self-antigens in the intestine. However, their precise properties and functions in the gut, as well as the molecular basis of their recruitment to the gut, are poorly understood. Here, we found that most of the CD4(+)CD25(+) T cells in the small intestinal lamina propria (LP) express Foxp3 and exhibit an 'effector/memory' phenotype, CD44(hi)CD45RB(lo)CD62L(-), whereas only a minority of the Foxp3(+)CD4(+)CD25(+) T cells in the spleen and mesenteric lymph nodes showed this phenotype. The Tregs in the small intestinal LP (LP-Tregs) expressed higher levels of CCR4 and CCR9 and a substantially lower level of CCR7 than the Tregs in the spleen. In vitro, the LP-Tregs showed chemotaxis to CCL25/thymus-expressed chemokine. In addition, they showed efficient chemotaxis to the CCR4 ligands, CCL17/thymus and activation-regulated chemokine and CCL22/macrophage-derived chemokine, which are abundantly expressed by dendritic cells (DCs) in the small intestinal LP. In vivo, approximately 50% of the LP-Tregs were closely associated or in direct contact with LP-DCs. These findings demonstrate that LP-Tregs are phenotypically and functionally unique and raise the possibility that they are retained in the small intestinal LP through the action of CCL17 and CCL22, which are locally produced by LP-DCs.
Guo
Zijin
Z
Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Jang
Myoung Ho
MH
Otani
Kazuhiro
K
Bai
Zhongbin
Z
Umemoto
Eiji
E
Matsumoto
Masanori
M
Nishiyama
Mika
M
Yamasaki
Mikako
M
Ueha
Satoshi
S
Matsushima
Kouji
K
Hirata
Takako
T
Miyasaka
Masayuki
M
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D054414:Chemokine CCL17 / Q000276:immunology; D054422:Chemokine CCL22 / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005786:Gene Expression Regulation; D007156:Immunologic Memory / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015703:Antigens, CD; D060908:CTLA-4 Antigen; D054414:Chemokine CCL17; D054422:Chemokine CCL22; C556707:Ctla4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D019707:Receptors, Chemokine