Modulation of lymphokine release and cytolytic activities by activating peripheral blood lymphocytes via CD2.
We had previously shown that the signal of activation delivered via CD2 varies according to the mitogenic pair of CD2 mAb used. We had selected two typical mAb pairs, D66 + T11(1) and GT2 + T11(1), the former delivering the "richest" signal, the latter the poorest. Here we analyzed the cytolytic activities generated within PBL-stimulated by these two pairs. When purified CD2+,3- cells were cultured with either one of these two pairs, no significant lymphokine-activated killer (LAK) activity--namely the activity exerted on NK-resistant malignant cell lines or fresh tumor cells--was detected, thereby demonstrating the inability of CD2 mAb pairs to directly trigger the LAK precursors. By contrast, when purified CD2+,3+ cells were cultured, only D66 + T11(1) was able to trigger a potent CTL activity, as judged by targeting their activity, at the effector phase, with a bridging CD3 mAb on a FcR+ target cell or by using heteroaggregates on FcR- malignant cells. When whole PBL were used, a similar and moderate LAK activity was generated after culture with either one of the 2 CD2 mAb pairs. This, in fact, masked quite different events. The amounts of endogeneous IL-2 released in PBL cultures with GT2 + T11(1) was rather low, although it was sufficiently high in PBL cultures with D66 + T11(1) to generate a potent LAK activity. Yet, PBL stimulated with D66 + T11(1) released concomitantly a high amount of IL-4 which inhibited the development of the LAK activity, as demonstrated by unmasking this activity with an anti-IL4 antiserum and which did not inhibit the T CTL activity; this IL-4 secretion was not seen with GT2 + T11(1). Therefore, stimulation by these two typical CD2 mAb pairs induce a striking different pattern of IL synthesis.
Valentin
H
H
Laboratoire d'Immunologie des Tumeurs de l'Enfant, Institut Gustave-Roussy, Lyon, France.
Groux
H
H
Gelin
C
C
Chretien
I
I
Bernard
A
A
D000937:Antigen-Antibody Reactions; D015703:Antigens, CD / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000502:physiology*; D018801:CD2 Antigens; D017252:CD3 Complex; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000096:biosynthesis; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D011971:Receptors, Immunologic / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015847:Interleukin-4