The cascading, interrelated roles of interleukin-1, interleukin-2, and interleukin-6 in murine anti-CD3-driven T cell proliferation.
T cell stimulation occurs following interaction of T cell receptor (TcR) with processed antigen presented by autologous accessory cells (AC). The effects of antigen stimulation on T cells are mimicked by monoclonal antibodies (Mabs) defining proteins of the TcR-CD3 complex. In this study, we examine the roles of T cell density, AC density, divalent and polyvalent forms of anti-CD3 Mab, and the cytokines interleukin (IL)-1, IL-2, and IL-6 in T cell activation and proliferation. Stringently AC-depleted T cells do not proliferate in response to Con A or divalent anti-CD3; however, polyvalent anti-CD3 provides a powerful signal for isolated resting T cell proliferation. Recombinant (r)IL-2 strongly amplifies T cell proliferation in response to anti-CD3, whereas rIL-1 exerts no direct effects on anti-CD3-stimulated T cells. In the presence of AC, however, rIL-1 augments T cell proliferation to anti-CD3. Recombinant IL-6 promotes T cell proliferation among T cells stimulated with polyvalent but not divalent anti-CD3. As deduced by Northern blot analysis, rIL-1 increases cytoplasmic levels of IL-6 mRNA in AC. Recombinant IL-6, in turn, amplifies the accumulation of stable IL-2 transcripts in purified T cells stimulated with polyvalent anti-CD3. Hence, IL-1, IL-6, and IL-2 support T cell proliferation through cascading effects at the level of gene transcription. The cytokines evaluated in this study, however, do not fully reconstitute AC functions in promoting anti-CD3 Mab T cell proliferation.
Pankewycz
O G
OG
Charles A. Dana Research Institute, Harvard-Thorndike Laboratory, Beth Israel Hospital, Boston, Massachusetts 02215.
Yui
M
M
Kelley
V E
VE
Strom
T B
TB
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000235:genetics / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology*; D015290:Second Messenger Systems; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins