IL-12 augments antigen-dependent proliferation of activated T lymphocytes.
Ag-dependent T cell activation requires multiple transmembrane signals including activation of Ag-specific T cell receptor in combination with signals delivered through cytokine receptors. IL-12 is a heterodimeric cytokine involved in the regulation of NK and T lymphocyte responses. In examining the role of IL-12 in T cell activation, we found a direct relationship between Ag stimulation and IL-12-induced proliferation. Unlike IL-2, which induced proliferation of CTL either in the presence or absence of a CD3/TCR co-signal, IL-12 mediated proliferation of CTL only when the cells were recently co-stimulated with alloantigen or solid-phase anti-CD3 antibody. After culture in the absence of alloantigen or anti-CD3 for 7 to 14 days, these CTL lost the ability to proliferate to IL-12 alone. Under these conditions, however, IL-12 synergized with low-dose IL-2 to induce CTL proliferation. Restimulation with alloantigen or solid-phase anti-CD3 restored the ability of the CTL to proliferate to IL-12 alone. Not all Ag signals resulted in IL-2 independent proliferation to IL-12. For example, CTL with specificity for influenza matrix peptide proliferated best when co-cultured with peptide Ag presented on self MHC and a combination of IL-2 and IL-12. This evidence suggests that IL-12 may be useful in expanding an Ag-specific T cell population, as the culture of CTL with IL-12 and low-dose IL-2 leads to proliferation only in response to an Ag co-signal.
Department of Surgery, Brigham and Women's Hospital, Boston, MA.
M M
MM
Bertagnolli
B Y
BY
Lin
D
D
Young
S H
SH
Herrmann
D000595:Amino Acid Sequence; D017252:CD3 Complex / Q000502:physiology; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007111:Immunity, Cellular; D018664:Interleukin-12; D007376:Interleukin-2 / Q000502:physiology; D007378:Interleukins / Q000502:physiology*; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000276:immunology
D017252:CD3 Complex; D007376:Interleukin-2; D007378:Interleukins; D007519:Isoantigens; C031540:M-protein, influenza virus; D014763:Viral Matrix Proteins; D018664:Interleukin-12