CD40 Ligand--an anti-apoptotic molecule in Hodgkin's disease.
The expression of CD40L was investigated in HD involved lymph nodes by flow cytometry (FCM) and reverse transcriptase polymerase chain reaction (RT-PCR). Also an investigation of the role of CD40L in upregulation of the anti-apoptotic gene BclxL in a Hodgkin's disease (HD) derived cell line was undertaken. HD patients (n = 18) had significantly higher numbers of activated CD4+ and CD8+ T cells in the tumor microenvironment as compared to controls (n = 8). HD patients also demonstrated higher numbers of CD4+, CD8+ and CD19+ lymphocytes co-expressing CD40L as compared to controls. The CD40L signal was consistently and significantly upregulated in HD patients (n = 5) as compared to controls (n = 3) at the mRNA level. RT-PCR and FCM analysis revealed that soluble CD40L upregulated BclxL levels in the Fas-sensitive HD cell line HDLM2. We conclude that CD40L can act as an important anti-apoptotic molecule by upregulating BclxL expression in Reed-Sternberg cells of HD and may be partly responsible for their survival 'in-vivo'.
Immunology Division, Cancer Research Institute, Tata Memorial Centre, Parel, Mumbai 400 012, India.
S S
SS
Metkar
P P
PP
Manna
M
M
Anand
K N
KN
Naresh
S H
SH
Advani
J J
JJ
Nadkarni
D017209:Apoptosis / Q000502:physiology*; D023201:CD40 Ligand / Q000502:physiology*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000473:pathology*; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D019310:Pseudolymphoma / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051020:bcl-X Protein; D023201:CD40 Ligand