Co-expression of CD4 and CD8 associated with elevated interleukin-4 in a cord T cell line derived by cocultivating normal cord leukocytes and an HTLV-II-producing simian leukocyte cell line (Si-IIA)

Abstract

A new interleukin-2(IL-2)-dependent T cell line, designated CS-IIA, was established by co-cultivating normal human cord leukocytes and a lethally X-irradiated HTLV-II-producing simian leukocyte cell line (Si-IIA). CS-IIA showed CD4 dominance during the early culture. However, after addition of IL-2, CS-IIA predominantly co-expressed CD4 and CD8 (69.5%) and also expressed the surface markers CD1-, CD3+, CD19-, CD25+ and HLA-DR+. A significantly elevated level of IL-4 (1697 pg/ml) was observed in the culture supernatant from CS-IIA. In addition, the conversion of phenotype from some CD4+CD8+ cells to CD4+CD8- was demonstrated by the neutralization assay using anti-IL-4 antibody. CS-IIA had a normal human karyotype and was free from Epstein-Barr virus nuclear antigen and immunoreactive with sera of HTLV-I- or HTLV-II-infected patients and anti-HTLV-1, p19 or p24 mAb. The provirus genome of HTLV-II was detected in this cell line by the polymerase chain reaction combined with a digoxigenin-enzyme-linked immunosorbent assay. However, electron microscopy of CS-IIA cells revealed no C-type virus particles in the extracellular space. These results indicate that HTLV-II can be transmitted from an HTLV-II-infected simian leukocyte cell line to human cord T lymphocytes and suggest that co-expression of CD4 and CD8 on T cells may be induced by the high level of IL-4, which can mediate CD8 induction on CD4+ T cell clones.

Circulating CD4+CD8+ T lymphocytes in patients with Kawasaki disease

“…Regarding the mechanisms that lead mature T cells to become CD4 + CD8 + T cells, several studies suggest the contribution of IL‐4 to this process. This concept is supported by the following observations: the expression of CD8 + antigen was induced in CD4 + T cell clones stimulated by IL‐4 [25], and the increase of IL‐4 production in CD4 + CD8 + T cell lines, established by co‐culturing normal cord leucocytes and Si‐IIA, was observed [23]. Regarding the correlation between KD and IL‐4, we have found that the plasma IL‐4 concentration reaches a maximum in the acute KD phase, and returns to normal in the convalescent phase [6].…”

“…The correlation between virus infection and the appearance of CD4 þ CD8 þ T cells was also observed in patients with disorders [23]. Lusso et al reported that the expression of CD4 antigen was induced when CD8 þ T cells were infected with human herpes virus 6 [24].…”

“…Hayashi et al . demonstrated that a CD4 + CD8 + T cell line could be established when normal cord leucocytes were co‐cultured with a human T lymphotropic virus type II‐producing simian leucocyte cell line (Si‐IIA) [23]. Lusso et al .…”

Rabbit Model for Human EBV-Associated Hemophagocytic Syndrome (HPS)

“…This rabbit model was initially established by chance via studies of the HTLV-II-infected cynomolgus cell line (Si-IIA). 42,43,55 The direct causative relationship between infection by EBV-like viruses (cynomolgus-EBVs, 32,33 HVMA, 53 and HVMNE 54 ) and the subsequent development of ML is very clear in the EBV-like virusinfected rabbit experimental models, reinforcing the assertion that EBV plays a significant role in the development of EBV-associated tumors. According to the comparative overview data of EBV-associated diseases in human and rabbits (Tables 4 and 5), these rabbit lymphomas induced by simian EBV-like viruses are very good models for the fatal T-cell LPD seen in fatal infectious mononucleosis/fatal LPD with EBV-AHS or EBVpositive T-cell lymphoma.…”

An animal model for Epstein–Barr virus (EBV)‐associated lymphomagenesis in the human: Malignant lymphoma induction of rabbits by EBV‐related herpesvirus from cynomolgus

“… 20 Si‐IIA cells immortalize human T cells. 21,22 During a study on the prevention of HTLV‐II infection using Si‐IIA, we found by chance that malignant lymphoma develops in Japanese white rabbits when they were inoculated intravenously and that these rabbit lymphomas had no integration of HTLV‐II genome. 23 Later a type of oncogenic virus, EBV‐related herpesvirus in Si‐IIA cells (Si‐IIA‐EBV) was identified, and malignant lymphomas induced by Si‐IIA in Japanese white rabbits as well as New Zealand white rabbits contained EBV‐related DNA.…”