Human T cell responses to IL-1 and IL-6 are dependent on signals mediated through CD2.
We investigated the involvement of IL-1 and IL-6 in activation of resting human T lymphocytes via the Ti-Ag receptor/CD3-dependent and the CD2-dependent pathways, respectively. When lymphocytes were triggered through CD3-Ti, neither IL-1 nor IL-6 nor the combination of both cytokines was capable of inducing a proliferative response, whereas addition of monocytes or IL-2 to such a system mediated DNA synthesis and cellular mitosis. In contrast, in the presence of submitogenic concentrations of mAb directed at CD2, IL-1 and/or IL-6 produced marked comitogenic dose-dependent effects. Moreover, although the action of IL-1 was clearly dependent on expression of the IL-2/IL-2R system, proliferation to CD2 antibody plus IL-6 could not be blocked by mAb directed at the IL-2R and/or IL-4. T cell responsiveness to both IL-1 and IL-6 was facilitated in the presence of CD58-like signals as delivered by human rCD58, SRBC or a mAb (anti-T111A), which binds to an interaction site for CD58 on the human CD2 molecule. These findings indicate that CD2 and its ligand CD58 play an important role in T cell/monocyte interactions during primary immune responses by means of upregulating T cell susceptibility to monocyte-derived cytokines.
Endler-Jobst
B
B
Abtlg. Angewandte Immunologie, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany.
Schraven
B
B
Hutmacher
B
B
Meuer
S C
SC
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018801:CD2 Antigens; D017252:CD3 Complex; D018968:CD58 Antigens; D002455:Cell Division / Q000276:immunology; D004261:DNA Replication / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008938:Mitosis / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D018968:CD58 Antigens; D007375:Interleukin-1; D015850:Interleukin-6; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic