Generation of helper and cytotoxic CD4+T cell clones specific for the minor histocompatibility antigen H-Y, after in vitro priming of human T cells by HLA-identical monocyte-derived dendritic cells.
BACKGROUND
There is now convincing evidence that minor histocompatibility antigens (mHag) may play a significant role in the pathogenesis of graft-versus-host disease after HLA-identical bone marrow transplantation. Indeed, in this clinical situation, T cells specific for mHag have been isolated. Here, we addressed whether one can generate mHag-specific T cells in vitro, without any in vivo immunization, among healthy blood donors.


METHODS
We used monocyte-derived dendritic cells (Mo-DCs) as antigen presenting cells to induce primary responses between healthy HLA-identical siblings, in mixed lymphocyte dendritic cell reactions (MLDCRs).


RESULTS
We show that CD4+ T-cell clones, specific for the mHag H-Y, can be generated in vitro. These clones were derived from a gender-mismatched positive MLDCR pair of HLA-identical siblings and were restricted by the HLA DQB1*0502 molecule. In addition, these CD4+ T clones were also able to lyse allogeneic targets with the same pattern of restriction and specificity than helper function. Finally, acute myeloid leukemia (AML) blast cells were susceptible to lysis by these clones.


CONCLUSIONS
Altogether, these results predict that Mo-DCs could help to generate class II-associated, mHag-specific, T-cell lines or clones in vitro, between healthy blood donors, without any need of transplantation-mediated immunization.
Eljaafari
A
A
Banque de Tissus et Cellules, Pavillon I, Hopital E. Herriot, 5 place d'Arsonval, 69003 Lyon, France. assia.eljaafari@efsrhonealpes.org
Farre
A
A
Duperrier
K
K
Even
J
J
Vie
H
H
Michallet
M
M
Souillet
G
G
Catherine Freidel
A
A
Gebuhrer
L
L
Rigal
D
D
D000208:Acute Disease; D000938:Antigen-Presenting Cells / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002455:Cell Division; D002460:Cell Line; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes; D005260:Female; D006182:H-Y Antigen / Q000032:analysis*; D006680:HLA Antigens / Q000032:analysis*; D006683:HLA-DQ Antigens / Q000032:analysis; D059866:HLA-DQ beta-Chains; D006801:Humans; D007951:Leukemia, Myeloid / Q000473:pathology / Q000503:physiopathology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D009000:Monocytes / Q000166:cytology*; D012727:Sex Characteristics; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology*
D000939:Epitopes; D006182:H-Y Antigen; D006680:HLA Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen