Adhesion molecules on MHC-nonrestricted lymphocytes: high density expression and role in oncolysis.
We have shown that interleukin-2 (IL-2) -activated adherent lymphocytes (A-LAK) display superior oncolytic activity against acute myelogenous leukemia (AML) blasts when compared to conventionally prepared lymphocytes with lymphokine-activated killing (LAK) activity. The A-LAK activity was generated promptly and from donors whose lymphocytes did not display any LAK activity. In comparison to LAK, a higher percentage of A-LAK expressed the CD25 and HLA class II (HLA-DR) activation-associated structures and high density of HLA class I antigens. Most striking, however, was the observation that lymphocytes from A-LAK cultures consistently contained a high density of CD2, CD11a, and CD18 adhesion molecules, as indicated cytometrically by their "bright" fluorescence intensity. Three color flow cytometric analysis indicated that virtually all CD56+,CD3- natural killer (NK) and CD56+,CD3+ T cells in unstimulated, LAK and A-LAK populations displayed this "bright" phenotype, while most CD56-,CD3+ T cells (with the exception of the small proportion found in A-LAK) were of the "dim" phenotype. The A-LAK cultures also contained a higher percentage of lymphocytes expressing CD11b (CR3 receptor) and CD54 (ICAM-1) antigens. The CD11a, CD18, and partially CD2 molecules were important in the A-LAK cytolytic mechanism against AML, since blocking of these structures with monoclonal antibodies (MAb) significantly decreased the antileukemia effect. Additionally, the ability of A-LAK to adhere to plastic was most strongly inhibited by anti-CD11a MAb and less, but significantly, by MAb against CD2, CD18, and CD56 molecules.(ABSTRACT TRUNCATED AT 250 WORDS)
Savary
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Department of General Surgery, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Lotzová
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D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis*; D015815:Cell Adhesion Molecules / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008285:Major Histocompatibility Complex
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D007376:Interleukin-2