Human t cell-replacing factor(s): a comparison of recombinant and purified human b cell growth and differentiation factors

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Abstract
Conditioned medium from phytohemagglutinin‐activated T cells contains T cell‐replacing factor(s) (TRF) able to restore specific antibody responses by human blood or tonsillar B cells which have been thoroughly depleted of T cells. Of twelve recombinant cytokines tested as possible candidates for TRF in conditioned media, namely human recombinant interleukin (hrIL) 1α and β, hrIL2, hrIL3, hrIL4, hrIL5, hrIL6, hr1FN‐α and ‐γ, hr granulocyte macrophage colony‐stimulating factor (hrGM‐CSF) and tumor necrosis factor (hr TNF)‐α and ‐β only IL2 was found to have TRF activity. In addition, a semi‐purified low molecular weight B cell growth factor (BCGFlow) also had TRF activity. As the commercially available BCGFlow is known to contain low concentrations of IL2, IFN‐γ, TNF and GM‐CSF as impurities, it was important to exclude these as being responsible for the TRF activity. At the concentrations present in BCGFlow (low was unlikely to be due to such a synergistic combination of cytokines for the following reasons. First, in several experiments, responses were obtained with BCGFlow, but not with IL2 or combinations of IL2 with IFN and TNF. Second, antibody to IL2 was found to inhibit the TRF activity of IL2 but not of BCGFlow. Taken together these findings show that two distinct cytokines (IL2 and BCGFlow) are TRF for human B cells. However, some combinations of cytokines can also have TRF activity underlining the complexities which can arise from working with semi‐purified rather than recombinant factors.