Essential role of OX40L on B cells in persistent alloantibody production following repeated alloimmunizations.
OX40/OX40 ligand (OX40L) interactions are implicated in costimulation for both CD4(+) T and B cells in a bidirectional manner. To determine the role of OX40/OX40L interactions in recipient antidonor responses after multiple allogeneic transfusions, we examined alloreactive cytotoxic T lymphocyte (allo-CTL) activity and alloantibody production in repeatedly alloimmunized OX40L-deficient mice. After the fifth alloimmunization, whereas OX40L-deficient mice showed allo-CTL activity with levels comparable to those of wild-type mice, alloantibody production in OX40L-deficient mice was significantly reduced, accompanied by fewer memory B and CD4(+) T cells with reduced function. Furthermore, nu/nu mice that received OX40L-deficient T cells still exhibited impaired alloantibody production with fewer memory CD4(+) T and B cells. In contrast, RAG-2-deficient mice that received both wild-type T cells and OX40L-deficient B cells produced scant alloantibodies with fewer memory B cells, but sufficient memory CD4(+) T cells. Thus, OX40L on B cells, rather than on T cells, is apparently required for adequate and persistent production of alloantibodies after repeated alloimmunizations.
Kato
Hiroshi
H
Division of Immunology, Institute for Medical Science, Dokkyo University School of Medicine, Tochigi, Japan.
Kojima
Hidefumi
H
Ishii
Naoto
N
Hase
Hidenori
H
Imai
Yutaka
Y
Fujibayashi
Takashi
T
Sugamura
Kazuo
K
Kobata
Testuji
T
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D001803:Blood Transfusion; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D007114:Immunization; D007156:Immunologic Memory; D007518:Isoantibodies / Q000097:blood*; D007519:Isoantigens / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D053278:OX40 Ligand; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D048069:Tumor Necrosis Factors
D007518:Isoantibodies; D007519:Isoantigens; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors