Characterization of a novel subset of CD8(+) T cells that expands in patients receiving interleukin-12.

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  • Additional Information
    • Source:
      Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Print ISSN: 0021-9738 (Print) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
    • Publication Information:
      Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
      Original Publication: New Haven [etc.] American Society for Clinical Investigation.
    • Subject Terms:
      CD8-Positive T-Lymphocytes/*drug effects ; Immunologic Factors/*pharmacology ; Interleukin-12/*pharmacology ; T-Lymphocyte Subsets/*drug effects; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/ultrastructure ; Cell Division/drug effects ; Gene Expression Regulation/drug effects ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; Humans ; Immunologic Factors/therapeutic use ; Immunologic Memory ; Interferon-gamma/biosynthesis ; Interferon-gamma/genetics ; Interleukin-12/therapeutic use ; Interleukin-2/pharmacology ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; Receptors, Antigen, T-Cell, alpha-beta/genetics ; Receptors, Interleukin/biosynthesis ; Receptors, Interleukin/genetics ; Receptors, Interleukin-12 ; Receptors, Interleukin-2/biosynthesis ; Receptors, Interleukin-2/genetics ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/ultrastructure ; Up-Regulation/drug effects
    • Abstract:
      IL-12 has significant antitumor activity in mice that may be mediated by CD8(+) T cells. We show in this report that repeated subcutaneous injections of IL-12 in patients with cancer resulted in the selective expansion of a subset of peripheral blood CD8(+) T cells. This T cell subset expressed high levels of CD18 and upregulated IL-12 receptor expression after IL-12 treatment in vivo. In normal subjects, these CD3(+)CD8(+)CD18(bright) T cells expressed IL-12 and IL-2 receptors and adhesion/costimulatory molecules to a greater degree than other CD8(+) and CD4(+) T cells. They appeared morphologically as large granular lymphocytes, although they did not express NK cell markers such as CD56. In addition, CD8(+)CD18(bright) T cells were almost exclusively T cell receptor (TCR) alphabeta+, and exhibited a TCR Vbeta repertoire that was strikingly oligoclonal, whereas the Vbeta repertoire of CD18(dim) T cells was polyclonal. Although CD8+CD18(bright) T cells demonstrated little functional responsiveness to IL-12 or IL-2 alone in vitro, they responded to the combination of IL-12+IL-2 with strong IFN-gamma production and proliferation and enhanced non-MHC-restricted cytolytic activity. In contrast, CD18(dim) T cells were not activated by IL-12 or IL-2, alone or in combination. These findings demonstrate that CD8+CD18(bright) T cells are a unique population of peripheral blood lymphocytes with features of both memory and effector cells that are capable of TCR-independent activation through combined stimulation with IL-12+IL-2. As this activation results in IFN-gamma production and enhanced cytolytic activity, these T cells may play a role in innate as well as acquired immunity to tumors and infectious pathogens. Additional studies will be necessary to determine whether CD8+CD18(bright) T cells mediate the antitumor effect of IL-12 or IL-2 administered to cancer patients, and if so, whether maximal activation of these T cells with the combination of IL-12+IL-2 in vivo can augment the clinical effectiveness of these cytokines.
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    • Grant Information:
      CA41619 United States CA NCI NIH HHS
    • Accession Number:
      0 (Immunologic Factors)
      0 (Interleukin-2)
      0 (Receptors, Antigen, T-Cell, alpha-beta)
      0 (Receptors, Interleukin)
      0 (Receptors, Interleukin-12)
      0 (Receptors, Interleukin-2)
      187348-17-0 (Interleukin-12)
      82115-62-6 (Interferon-gamma)
    • Publication Date:
      Date Created: 19980806 Date Completed: 19980826 Latest Revision: 20181113
    • Publication Date:
      20231215
    • Accession Number:
      PMC508917
    • Accession Number:
      10.1172/JCI3861
    • Accession Number:
      9691093