Depletion of activated Vbeta8+ T cells disrupts bispecific antibody directed antitumor immunity.
BACKGROUND
Activation of Vbeta8+ T cells with superantigen staphylococcal enterotoxin B (SEB) and use of an antitumor, anti-CD3 bispecific antibody (BsAb) leads to tumor protective immunity. We hypothesize that Vbeta8+ T-cell activation in combination with BsAb is crucial for tumor protective immunity in this model.


METHODS
Adolescent C3H/HeN mice were intravenously injected with syngeneic CL62 melanoma to establish pulmonary metastasis. Three days after establishing pulmonary metastasis, predominantly Vbeta8+ T cells are activated with 50 mug of intraperitoneal superantigen SEB. T cells were depleted at different time points in relation to SEB administration to assess the effect on protective immunity against a second tumor challenge.


RESULTS
Protective immunity is significantly (P < 0.008) decreased when Vbeta8+ depletion occurs 6 h after SEB injection, as growth of rechallenged CL62 melanoma occurred in 43%. Protective immunity is present at all other time points when mice survive Vbeta8+ T-cell depletion. Survival of animals treated with SEB/BsAb (82%) is significantly better (P < 0.002) than with SEB alone (60%) or nontreated control (0%). Survival when Vbeta8+ T-cell depletion occurred at 6 h and 48 h post-SEB is 72% and 77%, respectfully, and is statistically indistinguishable (P < 0.232 and P < 0.602). If T-cell depletion was conducted before SEB administration, however, the combination of SEB and BsAb did not result in significant protective immunity. T-cell depletion before the use of SEB alone, without BsAb, failed to result in significant protective immunity.


CONCLUSIONS
Depletion of Vbeta8+ T cells 6 h after activation disrupts the development of protective immunity.
McConnell
Elizabeth J
EJ
Arizona State University, Arizona Biodesign Institute, Tempe, Arizona, USA. msemcconnell@hotmail.com
McLemore
Elisabeth C
EC
Talac
Robert
R
Joshi
Lokesh
L
Nelson
Heidi
H
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000172:deficiency; D004768:Enterotoxins / Q000494:pharmacology; D007109:Immunity; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008545:Melanoma / Q000276:immunology* / Q000556:secondary; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D018089:Superantigens / Q000494:pharmacology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors
D018033:Antibodies, Bispecific; D017252:CD3 Complex; D016207:Cytokines; D004768:Enterotoxins; D007376:Interleukin-2; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma