Galectin-1 mediated suppression of Epstein-Barr virus specific T-cell immunity in classic Hodgkin lymphoma.
In Hodgkin lymphoma (HL), the malignant Hodgkin Reed-Sternberg cells interact with the host microenvironment to create an immunosuppressive network that protects the lymphoma from immune attack. These mechanisms are not fully understood. We examined the role of the immunomodulatory protein galectin-1 (Gal-1) on Epstein-Barr virus-specific CD8(+) T cell responses in HL. Initial studies indicated Gal-1 expression in all in vitro established Hodgkin Reed-Sternberg cell lines. In situ analysis revealed Gal-1 expression in 26 of 42 classic HL, whereas Gal-1 was uniformly negative in nodular lymphocyte predominant HL. Gal-1(hi) expression was associated with male gender, older patients, reduced CD8(+) T cell infiltration at the tumor site, and most importantly, an impaired latent membrane protein 1 and 2-specific CD8(+) T-cell responses. In vitro exposure to recombinant Gal-1 inhibited proliferation and interferon-gamma expression by Epstein-Barr virus-specific T cells. These observations provide an important link between the Gal-1-mediated immunomodulatory networks and loss of antigen-specific T-cell function in classic HL.
Gandhi
Maher K
MK
Australian Centre for Vaccine Development, Tumor Immunology Laboratory, Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane, Australia.
Moll
Guido
G
Smith
Corey
C
Dua
Ujjwal
U
Lambley
Eleanore
E
Ramuz
Olivier
O
Gill
Devinder
D
Marlton
Paula
P
Seymour
John F
JF
Khanna
Rajiv
R
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D005260:Female; D037483:Galectin 1 / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006689:Hodgkin Disease / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008297:Male; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes
D037483:Galectin 1; D011994:Recombinant Proteins; D007371:Interferon-gamma