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IL-2-independent generation of FOXP3(+)CD4(+)CD8(+)CD25(+) cytotoxic regulatory T cell lines from human umbilical cord blood.
Exp Hematol. 2007 Feb; 35(2):287-96.EH

Abstract

OBJECTIVE

Since the existence of mouse naturally occurring CD4(+)CD25(+) T regulatory (Treg) cells was demonstrated, a variety of human Treg subsets have been identified as distinct T cell populations. Here we show the establishment of novel Treg cell lines possessing unique characteristics.

METHODS

Novel Treg cell lines, designated HOZOT, were generated by coculturing human umbilical cord blood cells with mouse stromal cell lines in the absence of exogenous IL-2 or other cytokines. HOZOT were characterized and compared with CD4(+)CD25(+) Treg cells in terms of the CD phenotype, FOXP3 expression, suppressor activity against allogeneic MLR, anergy property, and IL-10 production.

RESULTS

HOZOT were generated and expanded as normal lymphoblastoid cells with cytotoxic activity against the cocultured stromal cells. HOZOT consisted of three subpopulations as defined by phenotype: CD4(+)CD8(+), CD4(+)CD8(dim), and CD4(-)CD8(+). All three subpopulations showed both suppressor and cytotoxic activities. While HOZOT's expression of FOXP3, CD25, GITR, and cytoplasmic CTLA-4 implied a similarity to naturally occurring CD4(+)CD25(+) Treg cells, these two Treg cells differed in IL-2 responsiveness and IL-10 production.

CONCLUSIONS

Our studies introduce a new method of generating Treg cells in an IL-2-independent manner and highlight a unique Treg cell type with cytotoxic activity and a phenotype of FOXP3(+)CD4(+)CD8(+)CD25(+).

Authors+Show Affiliations

Cell Biology Institute, Research Center, Hayashibara Biochemical Laboratories, Inc., Okayama, Okayama, Japan. shnakamu@hayashibara.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17258077

Citation

Nakamura, Shuji, et al. "IL-2-independent Generation of FOXP3(+)CD4(+)CD8(+)CD25(+) Cytotoxic Regulatory T Cell Lines From Human Umbilical Cord Blood." Experimental Hematology, vol. 35, no. 2, 2007, pp. 287-96.
Nakamura S, Suzuki M, Sugimoto A, et al. IL-2-independent generation of FOXP3(+)CD4(+)CD8(+)CD25(+) cytotoxic regulatory T cell lines from human umbilical cord blood. Exp Hematol. 2007;35(2):287-96.
Nakamura, S., Suzuki, M., Sugimoto, A., Tsuji-Takayama, K., Yamamoto, M., Otani, T., Inoue, T., Harashima, A., Okochi, A., Motoda, R., Yamasaki, F., Orita, K., & Kibata, M. (2007). IL-2-independent generation of FOXP3(+)CD4(+)CD8(+)CD25(+) cytotoxic regulatory T cell lines from human umbilical cord blood. Experimental Hematology, 35(2), 287-96.
Nakamura S, et al. IL-2-independent Generation of FOXP3(+)CD4(+)CD8(+)CD25(+) Cytotoxic Regulatory T Cell Lines From Human Umbilical Cord Blood. Exp Hematol. 2007;35(2):287-96. PubMed PMID: 17258077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-2-independent generation of FOXP3(+)CD4(+)CD8(+)CD25(+) cytotoxic regulatory T cell lines from human umbilical cord blood. AU - Nakamura,Shuji, AU - Suzuki,Motoyuki, AU - Sugimoto,Akira, AU - Tsuji-Takayama,Kazue, AU - Yamamoto,Mayuko, AU - Otani,Takeshi, AU - Inoue,Toshiya, AU - Harashima,Akira, AU - Okochi,Ayumi, AU - Motoda,Ryuichi, AU - Yamasaki,Fumiyuki, AU - Orita,Kunzo, AU - Kibata,Masayoshi, PY - 2006/07/27/received PY - 2006/09/20/revised PY - 2006/10/17/accepted PY - 2007/1/30/pubmed PY - 2007/12/6/medline PY - 2007/1/30/entrez SP - 287 EP - 96 JF - Experimental hematology JO - Exp Hematol VL - 35 IS - 2 N2 - OBJECTIVE: Since the existence of mouse naturally occurring CD4(+)CD25(+) T regulatory (Treg) cells was demonstrated, a variety of human Treg subsets have been identified as distinct T cell populations. Here we show the establishment of novel Treg cell lines possessing unique characteristics. METHODS: Novel Treg cell lines, designated HOZOT, were generated by coculturing human umbilical cord blood cells with mouse stromal cell lines in the absence of exogenous IL-2 or other cytokines. HOZOT were characterized and compared with CD4(+)CD25(+) Treg cells in terms of the CD phenotype, FOXP3 expression, suppressor activity against allogeneic MLR, anergy property, and IL-10 production. RESULTS: HOZOT were generated and expanded as normal lymphoblastoid cells with cytotoxic activity against the cocultured stromal cells. HOZOT consisted of three subpopulations as defined by phenotype: CD4(+)CD8(+), CD4(+)CD8(dim), and CD4(-)CD8(+). All three subpopulations showed both suppressor and cytotoxic activities. While HOZOT's expression of FOXP3, CD25, GITR, and cytoplasmic CTLA-4 implied a similarity to naturally occurring CD4(+)CD25(+) Treg cells, these two Treg cells differed in IL-2 responsiveness and IL-10 production. CONCLUSIONS: Our studies introduce a new method of generating Treg cells in an IL-2-independent manner and highlight a unique Treg cell type with cytotoxic activity and a phenotype of FOXP3(+)CD4(+)CD8(+)CD25(+). SN - 0301-472X UR - https://www.unboundmedicine.com/medline/citation/17258077/IL_2_independent_generation_of_FOXP3_+_CD4_+_CD8_+_CD25_+__cytotoxic_regulatory_T_cell_lines_from_human_umbilical_cord_blood_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0301-472X(06)00661-8 DB - PRIME DP - Unbound Medicine ER -