Leukocyte adherence inhibition to myelin basic protein by cancer patients' T-lymphocytes in association with class II major histocompatibility antigens on monocytes.
Patients' leukocytes were shown to react consistently in tube leukocyte adherence inhibition (LAI) assays with myelin basic protein (MBP) at optimal concentration, whereas control leukocytes were nonreactive. Mononuclear cells from patients with cancer gave positive LAI reactions with MBP, but separated T-lymphocytes, monocytes, and neutrophils did not. The mononuclear cell LAI responses were blocked by monoclonal antibody (MAb) to monomorphic determinant of class II major histocompatibility complex (MHC) antigens and to T4+ (Leu-3a+) and T3+ (Leu-4+) T-cell differentiation antigens but not by antibody to class I MHC antigens or T8+ (Leu-2a+) antigens. MBP was thus recognized by helper T-cells, requiring presentation in association with class II MHC determinants on monocytes. MAb to class I and class II MHC antigens and to T8+ (Leu-2a+), T4+ (Leu-3a+), and T3+ (Leu-4+) differentiation antigens did not negate LAI mediated by peripheral blood lymphocytes to organ-specific cancer neoantigens (OSN) of crude extracts of allogeneic cancer, which had previously been shown to react with cytophilic antibody on allogeneic monocytes. When membrane OSN and leukocytes were autologous, T8+ (Leu-2a+) phenotypic T-cells also mediated LAI that was blocked by anti-T8 (Leu-2a) and anti-T3 (Leu-4). LAI induced by MBP was also negated by drugs that antagonize thromboxane-leukotriene biosynthesis, indicating that, in common with other LAI reactions, the terminal mediators of nonadherence are oxidative metabolites of arachidonic acid. In addition to clarifying the role of MBP in the cellular in vitro immunoreactivity of cancer patients, the present observations have important implications for theories of LAI. Sensitized leukocytes have different mechanisms for the recognition of antigens in different forms, and the antigen-stimulated leukocytes produce mediators that in a final common pathway induce nonadherence of surrounding cells through leukotriene-like metabolites.
D M
DM
Thomson
W J
WJ
Halliday
K
K
Phelan
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000276:immunology / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D006649:Histocompatibility Antigens / Q000276:immunology*; D006801:Humans; D007957:Leukocyte Adherence Inhibition Test; D008285:Major Histocompatibility Complex; D009000:Monocytes / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D001095:Arachidonic Acids; D006649:Histocompatibility Antigens; D004676:Myelin Basic Protein; D016718:Arachidonic Acid