Characterization of T-regulatory cells, induced by immature dendritic cells, which inhibit enteroantigen-reactive colitis-inducing T-cell responses in vitro and in vivo

TY - JOUR

T1 - Characterization of T-regulatory cells, induced by immature dendritic cells, which inhibit enteroantigen-reactive colitis-inducing T-cell responses in vitro and in vivo

AU - Gad, Monika

AU - Kristensen, Nanna N

AU - Kury, Evelyn

AU - Claesson, Mogens Helweg

PY - 2004/12/1

Y1 - 2004/12/1

N2 - Regulatory T (Treg) cells, derived from co-cultures of unfractionated CD4(+) T cells and immature dendritic cells (DC), suppress enteroantigen-induced proliferation of CD4(+) CD25(-) T cells. The DC-induced Treg cells are a mixture of CD25(+) (10-20%) and CD25(-) (80-90%) T cells. However, all the suppressor activity in vitro and in vivo resides in the CD25(+) T-cell subset. The CD25(+) DC-induced Treg cells can inhibit enteroantigen-induced proliferation in vitro through a transwell membrane, and their function does not appear to depend on previous activation. DC-induced CD25(+) Treg cells display a naive phenotype, expressing high levels of CD45RB and l-selectin (CD62L). In addition, the DC-induced Treg cells mediate a stronger suppressive activity than prototype CD25(+) regulatory T cells. The DC-induced Treg cells, and hereof purified CD25(+) and CD25(-) T-cell fractions, were co-injected into severe combined immunodeficiency (SCID) mice with colitis-inducing CD4(+) CD25(-) T cells. Both unfractionated CD4(+) and purified CD25(+) Treg cells fully protected the recipients against the development of colitis. In contrast, co-transfer of fractionated CD25(-) T cells offered no protection against disease development. Enterobacterial antigen-exposed CD4(+) T cells of the protected mice secreted higher levels of interleukin-10 and lower levels of interferon-gamma than the unprotected mice. The present data demonstrate DC-induced CD4(+) CD25(+) Treg cells, which phenotypically and functionally differ from the generally accepted prototype of CD25(+) Treg cells. These data may initiate new procedures for the expansion of Treg cells for clinical use.

AB - Regulatory T (Treg) cells, derived from co-cultures of unfractionated CD4(+) T cells and immature dendritic cells (DC), suppress enteroantigen-induced proliferation of CD4(+) CD25(-) T cells. The DC-induced Treg cells are a mixture of CD25(+) (10-20%) and CD25(-) (80-90%) T cells. However, all the suppressor activity in vitro and in vivo resides in the CD25(+) T-cell subset. The CD25(+) DC-induced Treg cells can inhibit enteroantigen-induced proliferation in vitro through a transwell membrane, and their function does not appear to depend on previous activation. DC-induced CD25(+) Treg cells display a naive phenotype, expressing high levels of CD45RB and l-selectin (CD62L). In addition, the DC-induced Treg cells mediate a stronger suppressive activity than prototype CD25(+) regulatory T cells. The DC-induced Treg cells, and hereof purified CD25(+) and CD25(-) T-cell fractions, were co-injected into severe combined immunodeficiency (SCID) mice with colitis-inducing CD4(+) CD25(-) T cells. Both unfractionated CD4(+) and purified CD25(+) Treg cells fully protected the recipients against the development of colitis. In contrast, co-transfer of fractionated CD25(-) T cells offered no protection against disease development. Enterobacterial antigen-exposed CD4(+) T cells of the protected mice secreted higher levels of interleukin-10 and lower levels of interferon-gamma than the unprotected mice. The present data demonstrate DC-induced CD4(+) CD25(+) Treg cells, which phenotypically and functionally differ from the generally accepted prototype of CD25(+) Treg cells. These data may initiate new procedures for the expansion of Treg cells for clinical use.

KW - Animals

KW - Antigens, Bacterial

KW - CD4-Positive T-Lymphocytes

KW - Cell Division

KW - Cells, Cultured

KW - Coculture Techniques

KW - Colitis

KW - Cytokines

KW - Dendritic Cells

KW - Female

KW - Immunophenotyping

KW - Interleukin-2

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, SCID

KW - Receptors, Interleukin-2

KW - T-Lymphocyte Subsets

U2 - 10.1111/j.1365-2567.2004.01977.x

DO - 10.1111/j.1365-2567.2004.01977.x

M3 - Journal article

C2 - 15554928

SN - 0953-4954

VL - 113

SP - 499

EP - 508

JO - Immunology. Supplement

JF - Immunology. Supplement

IS - 4

ER -