Abstract
Inflammatory bowel diseases take chronic courses due to the expansion of colitogenic CD4+ cells. However, it is unclear whether the persistent disease is driven by continuous reactivation of colitogenic memory CD4+ cells to generate effector CD4+ cells or by continuous generation of effector CD4+ cells from naïve cells. To clarify this issue, we performed a series of sequential adoptive transfers of Ly5.2+ and Ly5.1+ CD4+CD45RBhigh cells into RAG-2-/- mice at different time points. We show here that the secondarily transferred CD4+CD45RBhigh cells can be converted to CD4+CD44highCD62L-IL-7Rα high effector-memory T cells even in the presence of pre-existing effector-memory CD4+ cells. Although the total cell numbers of CD4+ cells in established colitic mice were consistently equivalent irrespective of the number of primarily transferred cells, the ratio of primarily and secondarily transferred cells was dependent on the ratio of the transferred cell numbers, but not on the order of the transfer. Of note, we found that primarily transferred CD4+ cells produced significantly lower amounts of IFN-γ and IL-17 than CD4+ cells arising from secondary transfer. In conclusion, the continuous generation of colitogenic CD4+ cells that compensate for exhausted CD4+ cells may be one of the mechanisms involved in the persistence of colitis.
| Original language | English |
|---|---|
| Pages (from-to) | 1264-1274 |
| Number of pages | 11 |
| Journal | European Journal of Immunology |
| Volume | 38 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2008 May |
| Externally published | Yes |
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Keywords
- Colitis
- Colitogenic memory T cells
- Mucosal immunity
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Continuous generation of colitogenic CD4+ T cells in persistent colitis. / Tomita, Takayuki; Kanai, Takanori; Fujii, Toshimitsu; Nemoto, Yasuhiro; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Totsuka, Teruji; Sakamoto, Naoya; Watanabe, Mamoru.
In: European Journal of Immunology, Vol. 38, No. 5, 05.2008, p. 1264-1274.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Continuous generation of colitogenic CD4+ T cells in persistent colitis
AU - Tomita, Takayuki
AU - Kanai, Takanori
AU - Fujii, Toshimitsu
AU - Nemoto, Yasuhiro
AU - Okamoto, Ryuichi
AU - Tsuchiya, Kiichiro
AU - Totsuka, Teruji
AU - Sakamoto, Naoya
AU - Watanabe, Mamoru
PY - 2008/5
Y1 - 2008/5
N2 - Inflammatory bowel diseases take chronic courses due to the expansion of colitogenic CD4+ cells. However, it is unclear whether the persistent disease is driven by continuous reactivation of colitogenic memory CD4+ cells to generate effector CD4+ cells or by continuous generation of effector CD4+ cells from naïve cells. To clarify this issue, we performed a series of sequential adoptive transfers of Ly5.2+ and Ly5.1+ CD4+CD45RBhigh cells into RAG-2-/- mice at different time points. We show here that the secondarily transferred CD4+CD45RBhigh cells can be converted to CD4+CD44highCD62L-IL-7Rα high effector-memory T cells even in the presence of pre-existing effector-memory CD4+ cells. Although the total cell numbers of CD4+ cells in established colitic mice were consistently equivalent irrespective of the number of primarily transferred cells, the ratio of primarily and secondarily transferred cells was dependent on the ratio of the transferred cell numbers, but not on the order of the transfer. Of note, we found that primarily transferred CD4+ cells produced significantly lower amounts of IFN-γ and IL-17 than CD4+ cells arising from secondary transfer. In conclusion, the continuous generation of colitogenic CD4+ cells that compensate for exhausted CD4+ cells may be one of the mechanisms involved in the persistence of colitis.
AB - Inflammatory bowel diseases take chronic courses due to the expansion of colitogenic CD4+ cells. However, it is unclear whether the persistent disease is driven by continuous reactivation of colitogenic memory CD4+ cells to generate effector CD4+ cells or by continuous generation of effector CD4+ cells from naïve cells. To clarify this issue, we performed a series of sequential adoptive transfers of Ly5.2+ and Ly5.1+ CD4+CD45RBhigh cells into RAG-2-/- mice at different time points. We show here that the secondarily transferred CD4+CD45RBhigh cells can be converted to CD4+CD44highCD62L-IL-7Rα high effector-memory T cells even in the presence of pre-existing effector-memory CD4+ cells. Although the total cell numbers of CD4+ cells in established colitic mice were consistently equivalent irrespective of the number of primarily transferred cells, the ratio of primarily and secondarily transferred cells was dependent on the ratio of the transferred cell numbers, but not on the order of the transfer. Of note, we found that primarily transferred CD4+ cells produced significantly lower amounts of IFN-γ and IL-17 than CD4+ cells arising from secondary transfer. In conclusion, the continuous generation of colitogenic CD4+ cells that compensate for exhausted CD4+ cells may be one of the mechanisms involved in the persistence of colitis.
KW - Colitis
KW - Colitogenic memory T cells
KW - Mucosal immunity
UR - http://www.scopus.com/inward/record.url?scp=47049123789&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=47049123789&partnerID=8YFLogxK
U2 - 10.1002/eji.200737745
DO - 10.1002/eji.200737745
M3 - Article
C2 - 18412157
AN - SCOPUS:47049123789
VL - 38
SP - 1264
EP - 1274
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 5
ER -