The initial studies on T cell replacing factors were carried at a time when the complexity ofthe cell interactions in the B cell response to antigen had yet to be fully appreciated. The requirement for helper T cells was demonstrated by the studies of Claman and his colleagues, and by Mitchell, Miller, and others. The work of Mitchison, Rajewsky and other demonstrated that the T cells were also antigen-specific and that there was a need for "linked recognition". That is to say that the antigen determinants recognized by the T cell had to be physically associated with the antigen determinants recognized by the B cell. This was at first taken as evidence for a need for direct cell-cell interaction between T cell and B cell, but it was soon realized that the same experiments could be accommodated by a model in which T cell help was mediated by small amounts of a locally effective T cell mediator.That the response of T cell-depleted spleens could in fact be restored by T cellderived mediators was first demonstrated in our laboratory (Dutton et al. 1971) and by Schimpl & Wecker (1972). Our experiment made use ofthe observation that large numbers of T cells were activated when MHC-disparate lymphocytes were mixed and showed that mixed lymphocyte reaction (MLR) culture supernatants contained a T cell replacing factor. It was quickly shown that other culture supernatants of concanavalin A (Con A) or antigen-activated T cells contained a similar activity (Andersson et al. 1972).The picture became more complicated when it was shown that such culture supernatants would not replace T cells in all B cell responses. Thus it was shown that histocompatible antigen-specific T cells were required in the response of

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Recent experiments suggested that alpha‐protein (AFP) may have immunoregulatory properties and play a role in protecting the fetus from rejection by the mother. The present study was performed to determine whether purified human AFP, its molecular variants separated on Lens culinaris agglutinin, and fetal serum albumin showed immunoregulatory activiiy on in vitro transformation of normal human lymphocytes by mitogens or by allogeneic cells. Human AFP and fetal serum albumin were purified from human whole fetuses by immunoabsorption, followed by acid elution. AFP variants (HLI, HL2, HL3, HL4) were separated by lectin affinity chromatography. The proteins were tested in lymphocyte cultures stimulated by concanavalin A, phytohaemagglutinin and pokeweed mitogen and in mixed lymphocyte cultures. Four batches of AFP and one batch of fetal albumin, in the concentration range of 0‐100 μg/ml and in one experiment up to 2 mg/ml, had a stimulatory effect on lymphocytes. One batch of human AFP showed inhibitory effect with low reproducibility. The variants had a stimulatory effect except for HL3, which was found to be slightly inhibitory in phytohaemagglutinin stimulated cultures when compared with cultures without AFP, but there was no significant difference when compared with cultures in which AFP was replaced by its dialysate. Thus, the results reported here are not consistent with the conclusion that human AFP has a significant immunosuppressive effect on man. Hypotheses about causes of discrepancies are analysed.