Resting human peripheral blood lymphocytes can be activated to cytolytic function by antibodies to CD3 in the absence of exogenous interleukin-2.
We investigated the ability of anti-CD3 antibodies to activate resting human peripheral blood lymphocytes (PBL) to a cytolytic function. We found that two anti-CD3 antibodies, but not an anti-CD4, anti-CD8, or anti-CD2 antibody, could activate resting unseparated PBL to become killer cells in the absence of exogenous interleukin-2 (IL-2), although exogenous recombinant IL-2 (rIL-2) synergized with anti-CD3. We also found that these anti-CD3 antibodies were active in the absence of rIL-2 only when linked to a solid surface such as a Sepharose bead or a plastic tissue culture plate. Cytolytic activity was measured in several ways: (i) by the ability of activated PBL to lyse the NK-sensitive line K562, and (ii) by the ability of these cells to lyse a CD10+ (CALLA+), NK-resistant target in the presence of either concanavalin A (lectin-dependent lysis) or an anti-CD10-anti-CD3 heterodimer. At least two different types of cytolytic cells were activated by anti-CD3 antibodies, an NK-like cell, which was CD2+CD3-CD4-CD8-CD16+-NKH1a+, and a CTL-like cell, which was CD2+CD3+CD4-CD8+CD16-NKH1a-. The former cell lysed the K562 line and the latter cell lysed Namalwa in the presence of the anti-CD10-anti-CD3 heterodimer or concanavalin A. The NK-like cell was probably activated by endogenous IL-2 produced by the anti-CD3-activated CD3+ cells and both the NK and CTL-like cells required the presence of adherent cells for maximal activity. The dose response and the kinetics of anti-CD3 activation of PBL to cytolytic activity were also studied. The use of the anti-CD3-activated cytolytic cells as effectors in anti-CD3 heterodimer-mediated lysis of tumor cells may be a novel approach to the therapy of cancer, and a comparison with the well-studied rIL-2/lymphokine-activated killer (LAK) system is discussed.
Scott
C F
CF
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Lambert
J M
JM
Bolender
S
S
Blattler
W A
WA
D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007399:Interphase; D007694:Killer Cells, Natural / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000961:Antilymphocyte Serum; D007376:Interleukin-2; D011994:Recombinant Proteins