A major fraction of human bone marrow lymphocytes are Th2-like CD1d-reactive T cells that can suppress mixed lymphocyte responses.
Murine bone marrow (BM) NK T cells can suppress graft-vs-host disease, transplant rejection, and MLRs. Human BM contains T cells with similar potential. Human BM was enriched for NK T cells, approximately 50% of which recognized the nonpolymorphic CD1d molecule. In contrast to the well-characterized blood-derived CD1d-reactive invariant NK T cells, the majority of human BM CD1d-reactive T cells used diverse TCR. Healthy donor invariant NK T cells rapidly produce large amounts of IL-4 and IFN-gamma and can influence Th1/Th2 decision-making. Healthy donor BM CD1d-reactive T cells were Th2-biased and suppressed MLR and, unlike the former, responded preferentially to CD1d(+) lymphoid cells. These results identify a novel population of human T cells which may contribute to B cell development and/or maintain Th2 bias against autoimmune T cell responses against new B cell Ag receptors. Distinct CD1d-reactive T cell populations have the potential to suppress graft-vs-host disease and stimulate antitumor responses.
Exley
M A
MA
Cancer Biology Program, Hematology/Oncology, Beth Israel-Deaconess Medical Center, Bone Marrow Transplant Program, Harvard Skin Disease Research Center, Harvard Medical School, Boston, MA 02115, USA. mexley@caregroup.harvard.edu
Tahir
S M
SM
Cheng
O
O
Shaulov
A
A
Joyce
R
R
Avigan
D
D
Sackstein
R
R
Balk
S P
SP
D018949:Antigens, CD1 / Q000032:analysis*; D055610:Antigens, CD1d; D000954:Antigens, Surface / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type; D007959:Lymphocyte Culture Test, Mixed; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016176:T-Lymphocyte Subsets / Q000145:classification; D018418:Th2 Cells / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D000954:Antigens, Surface; C526877:CD1D protein, human; D016207:Cytokines; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B