Children with endemic Burkitt lymphoma are deficient in EBNA1-specific IFN-gamma T cell responses.
Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in equatorial Africa and is linked to Epstein-Barr virus (EBV) and Plasmodium falciparum coinfections early in life. Epstein-Barr nuclear antigen 1 (EBNA1) is the sole viral latent antigen expressed in BL tumors. Loss of EBNA1-specific immune surveillance could allow eBL emergence. Therefore, EBNA1-specific T cell responses were analyzed by IFN-gamma ELISPOT in Kenyan children with eBL and compared to healthy children with divergent malaria exposure. Significantly fewer children with eBL, 16% (7/44) had EBNA1-specific IFN-gamma responses in contrast to healthy children living in a malaria holoendemic area or in an area with sporadic malaria transmission, 67% (40/60) and 72% (43/60) responders, respectively (p < 0.003). Children with eBL maintained IgG(1) dominated antibody responses to EBNA1 similar to healthy children suggesting a selective loss of IFN-gamma secreting EBNA1-specific T cells in the presence of intact humoral immunity. CD8(+) T cell responses to EBV lytic and latent antigens not expressed in the tumors were similarly robust in eBL patients compared to healthy children. In addition, CD4(+) T cell responses to a malaria protein, merozoite surface protein 1, were present in lymphoma patients. This study demonstrates a selective loss of EBNA1-specific T cell responses in children with eBL and suggests a potential immunotherapeutic target for this EBV-associated lymphoma.
Moormann
Ann M
AM
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH.
Heller
Kevin N
KN
Chelimo
Kiprotich
K
Embury
Paula
P
Ploutz-Snyder
Robert
R
Otieno
Juliana A
JA
Oduor
Margaret
M
Münz
Christian
C
Rochford
Rosemary
R
D002051:Burkitt Lymphoma / Q000453:epidemiology* / Q000276:immunology* / Q000821:virology; D002648:Child; D019353:Endemic Diseases; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D007630:Kenya; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load
D019309:Epstein-Barr Virus Nuclear Antigens; D007074:Immunoglobulin G; D007371:Interferon-gamma; C417029:EBV-encoded nuclear antigen 1