Clonal analysis of peripheral blood lymphocytes from three patients with advanced neuroblastoma receiving recombinant interleukin-2 and interferon alpha.
In this study we have investigated, at the population and the clonal levels, the immunophenotypes and the non-specific cytotoxic functions of peripheral blood lymphocytes from three stage IV neuroblastoma patients receiving treatment with recombinant interleukin-2 (IL-2) and interferon alpha (IFN alpha). Both IL-2 alone and the combination of IL-2 and IFN alpha caused an in vivo expansion of CD56+, CD3- NK cells most of which expressed the p75 molecule, i.e. the beta chain of the IL-2 receptor. Peripheral blood mononuclear cells (PBMC), drawn after treatment, displayed an increased NK activity, but no lymphokine-activated killer (LAK) activity. However, the subsequent in vitro culture of PBMC with high-dose IL-2 induced the generation of a potent LAK activity, which was mediated by an expanded population of CD3+, CD8+ T cells. Finally lymphocytes that had been isolated after cytokine therapy were cloned, in the presence of low-dose phytohemagglutin, immediately or following culture with IL-2. Clones derived from LAK cells expanded in vitro had predominantly a CD3+, CD8+ immunophenotype, whereas those raised from freshly separated lymphocytes were either CD3+, CD4+ or CD3+, CD8+ in equal proportions. Most of the above clones were poorly or not at all cytolytic against NK-sensitive or NK-resistant targets. In contrast, the few NK clones obtained (CD3-, CD56+) lysed all targets with high efficiency.
Laboratory of Immunopathology, Scientific Institute G. Gaslini, Genova, Italy.
I
I
Prigione
P
P
Facchetti
E
E
Lanino
A
A
Garaventa
V
V
Pistoia
D015703:Antigens, CD / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology*; D009447:Neuroblastoma / Q000097:blood / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use
D015703:Antigens, CD; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins