Single cell studies have identified intraclonal heterogeneity of cytokine production by activated T cells. To investigate implications of cytokine heterogeneity for cell fate, an interleukin (IL)-2 promoter-green fluorescent protein (GFP) reporter transgenic model was developed to track IL-2+ and IL-2- T cells during differentiation from naive precursors. Antigen-activated IL-2+ and IL-2- cells had comparable proliferative capacities in primary responses. However, T cells that expressed IL-2 in primary responses demonstrated enhanced antigenic sensitivity and increased expression of effector cytokines in secondary responses in vitro and in vivo. Thus, heterogeneity of activation during a primary response translates into heterogeneous secondary responses, in which enhanced memory/effector function is linked to cells that previously exceeded an activation threshold associated with IL-2 gene transcription.
A cultured cell line (SHIN-3) derived from a human ovarian serous cystadenocarcinoma which consistently produces two tumor markers, CA-125 and tissue polypeptide antigen (TPA) was established. After 1 week of culture of 1 × 105 cells, high levels of tumor marker were observed (the total CA-125 release was 1,500 U and the total TPA release was 37.5 U). Expression of CA-125 and TPA was also demonstrated in cultured cells immunohistochemically. The volume of CA-125 release per cell was highest just before the start of the logarithmic growth phase. TPA production was increased in the logarithmic growth phase, but its relationship to the total number of cells was not clear.
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