Rat mitogen-stimulated lymphokine-activated T killer cells: production and effects on C6 glioma cells in vitro and in vivo in the brain of Wistar rats.
An in vitro technique was developed to generate activated rat T cells, with antitumor activity. Splenic mononuclear cells (SMC) from outbred Wistar and inbred Wistar-Munich rats were stimulated with Concanavalin A and recombinant human interleukin-2 (rIL-2) in vitro for 48 h. After 2 days, the nonadherent cells began proliferating and were maintained in rIL-2 for up to 18 days in vitro. FACScan analysis revealed that SMC was a mixture of cell types; however, CD5+ T cells rapidly increased and became the predominant cell type after 5 days in culture. SMC induced cytolysis of YAC-1, but not C6 glioma cells in 4 h 51Cr release assays. In contrast, 5- and 9-day T cells lysed C6 glioma and YAC-1 cells. The C6 cells were admixed with cultured effector cells at various effector-to-target (E:T) ratios and were injected into the right cerebral hemisphere of Wistar and Wistar-Munich rats for a Winn assay. Histopathologic evaluations revealed that a) SMC had no effect; b) 2- and 5-day T cells, injected at E:T ratios greater than 5:1, caused significant reduction in tumor size; and c) 2- or 5-day T cells, at a 40:1 E:T ratio, resulted in little or no histologic evidence of tumor. Eighty-three percent of animals receiving C6 and 5-day mitogen-stimulated lymphokine activated killer cells at an E:T ratio of 40:1 were alive 120 days postinjection (p less than 0.05).
Carson
W E
WE
Department of Surgery, Biochemistry, University of California, Irvine 92717.
Jakowatz
J G
JG
Yamamoto
R
R
Fitzgerald
T
T
Gupta
S
S
Vayuvegula
B
B
Lucci
J A
JA
Beckman
M T
MT
Dulkanchainun
S
S
Granger
G A
GA
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D008223:Lymphoma / Q000473:pathology; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011994:Recombinant Proteins; D003208:Concanavalin A