T cell activation following infection of primary follicle center lymphoma B cells with adenovirus encoding CD154.
Purified, high-titer adenovirus encoding murine CD154 (Ad-CD154) or human CD154 (Ad-hCD154) was used to infect lymph node cells isolated from patients with follicle center lymphoma. Infection of lymphoma B cells with Ad-CD154 at a multiplicity of infection (MOI) ratio of 100 or higher resulted in high-level transgene expression. Additionally, upon infection of lymphoma B cells, only Ad-CD154 resulted in surface expression of CD154, despite similar, high-level expression of either human or mouse CD154 by HeLa cells infected with Ad-hCD154 or Ad-CD154, respectively. Moreover, infection of lymphoma B cells with Ad-CD154, but not Ad-hCD154 or adenovirus encoding Eschericheria coli beta-galactosidase (Ad-LacZ), induced the neoplastic B cells to express higher levels of immune co-stimulatory molecules that are required for proficient presentation of antigen to T cells. Consistent with this, we found that Ad-CD154 infected lymphoma B cells could stimulate T cells to proliferate or produce interferon-gamma in allogeneic or autologous mixed lymphocyte interactions. We conclude that lymphoma B cells can be infected with Ad-CD154 and that this significantly enhances their recognition by allogeneic or autologous T cells. As such, Ad-CD154-transduced lymphoma B cells may have potential for the active immune therapy of patients with follicle center lymphoma.
Cantwell
M J
MJ
Immunogenex, Inc., La Jolla, CA, USA.
Wierda
W G
WG
Lossos
I S
IS
Levy
R
R
Kipps
T J
TJ
D000256:Adenoviridae; D000818:Animals; D023201:CD40 Ligand / Q000276:immunology*; D002455:Cell Division; D006367:HeLa Cells; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000821:virology; D051379:Mice; D010641:Phenotype; D013601:T-Lymphocytes / Q000502:physiology*
D023201:CD40 Ligand