CD4+CD25- T cells that express latency-associated peptide on the surface suppress CD4+CD45RBhigh-induced colitis by a TGF-beta-dependent mechanism.
Murine CD4(+)CD25(+) regulatory cells have been reported to express latency-associated peptide (LAP) and TGF-beta on the surface after activation, and exert regulatory function by the membrane-bound TGF-beta in vitro. We have now found that a small population of CD4(+) T cells, both CD25(+) and CD25(-), can be stained with a goat anti-LAP polyclonal Ab without being stimulated. Virtually all these LAP(+) cells are also positive for thrombospondin, which has the ability to convert latent TGF-beta to the active form. In the CD4(+)CD45RB(high)-induced colitis model of SCID mice, regulatory activity was exhibited not only by CD25(+)LAP(+) and CD25(+)LAP(-) cells, but also by CD25(-)LAP(+) cells. CD4(+)CD25(-)LAP(+) T cells were part of the CD45RB(low) cell fraction. CD4(+)CD25(-)LAP(-)CD45RB(low) cells had minimal, if any, regulatory activity in the colitis model. The regulatory function of CD25(-)LAP(+) cells was abrogated in vivo by anti-TGF-beta mAb. These results identify a new TGF-beta-dependent regulatory CD4(+) T cell phenotype that is CD25(-) and LAP(+).
Oida
Takatoku
T
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Zhang
Xingmin
X
Goto
Masao
M
Hachimura
Satoshi
S
Totsuka
Mamoru
M
Kaminogawa
Shuichi
S
Weiner
Howard L
HL
D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000378:metabolism; D019921:Biotinylation; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D003092:Colitis / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006041:Goats; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010446:Peptide Fragments / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D011498:Protein Precursors / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000096:biosynthesis*; D013194:Staining and Labeling; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D016212:Transforming Growth Factor beta / Q000502:physiology*; D053773:Transforming Growth Factor beta1
D000906:Antibodies; D016207:Cytokines; D010446:Peptide Fragments; D011498:Protein Precursors; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017493:Leukocyte Common Antigens