Requirements for the growth of T_H1 lymphocyte clones

Abstract

Besides the signal generated in a T lymphocyte after triggering the T cell receptor (TcR), most lymphocytes need a "second signal" to become fully activated. The necessity and nature of the "second signal" differs between different types of T cells. At the level of CD4-positive T helper lymphocytes interleukin 1 (IL 1) serves as "second signal" for those of the TH2 subtype (IL4, 5, 6 producer) but not for those of the TH1 subtype (IL 2, IFN-gamma producer). This correlates with the absence of the IL 1 receptor at the surface of TH1 clones. We report herein the further purification of T cell stimulating factor (TSF), a soluble mediator involved in the proliferation of TH1 lymphocytes. A preparation free of detectable IL 1, 2, 4 and IL 6 activity could act as "second signal" required for the growth of TH1 lymphocytes in a TcR-mediated, as well as a TcR-independent activation system. In addition, we suggest that IL 1 can influence the proliferation of TH1 clones in an indirect way, probably via the induction of TSF in accessory cells.

Interleukin‐12/T cell stimulating factor, a cytokine with multiple effects on T helper type 1 (Th1) but not on Th2 cells

“…Previously we reported that a TSF-containing supernatant as well as partially purified TSF can induce the proliferation of Con A or anti-CD3 activated T h l cells [33]. However, recombinant IL-12 failed to enhance the proliferation of KIIIS T h l cells activated with Con A whereas a crude TSF/IL-lZcontaining supernatant stimulated proliferation (Fig.…”

“…During the past few years we [32,331 and others [34,35] have presented evidence that there is also a soluble mediator which acts onThl cells.We have partially purified this factor provisionally termed T cell stimulating factor (TSF). TSF enhances IL-2 induced proliferation of mouse Thl cells [32,33] and is involved in the synthesis of IFN-y by T h l and NK cells [36]. IFN-y production by Thl cells can be initiated via theTcR (cyclosporin A-sensitive) [37] or by an alternative (cyclosporin A-resistant) pathway depending on the co-culture of T h l cells and M@ + IL-2 [38].…”

Components of an antigen‐/T cell receptor‐independent pathway of lymphokine production

“…From these data we draw the conclusion that TSF, in addition to its growth-promoting effects for T h l cells [14,16,211 is also participating in this alternative pathway of IFN-y production by T h l cells. TSF and a fixation-/UV light-resistant component of AC can induce the synthesis of IFN-y by several T h l clones.…”

“…This chemical modification of the AC could have destroyed the function of a membrane-bound contact molecule or the ability of the AC to release a soluble mediator required for the synthesis of IFN-y by theTh1 cells. In view of the finding that TSF functions as a co-stimulator in the antigenindependent stimulation of Thl cell proliferation [16] we tested whether this factor was also active in this pathway of IEW-y production and could perhaps restore the defect of carbodiimide-treated AC. The data presented in Table 1 demonstrate that this is indeed the case.…”

“…TheTcells were taken for the experiments at least 4 weeks after their last activation with syngeneic APC and antigen. They were propagated in v i m as described earlier [16]. The murine fibroblast line L929 was grown in IMDM containing 5% FCS.…”