Biomaterial Database

Enhancement of murine lymphokine-activated killer cell activity by retinoic acid. 1990

T H Lin, and T M Chu

Department of Diagnostic Immunology Research and Biochemistry, Roswell Park Memorial Institute, Buffalo, New York 14263.

Since retinoids have been suggested to be capable of potentiating immunity, the present study was undertaken to determine the effect, if any, on lymphokine-activated killer (LAK) cell activity by retinoic acid, an active metabolite of vitamin A and a differentiation enhancer. Retinoic acid alone was shown to induce no cytotoxicity generated from nylon wool-treated nonadherent murine (BALB/c) splenocytes against natural killer-resistant, LAK-sensitive syngeneic target tumor cells. When combined with human recombinant interleukin-2 (IL-2), retinoic acid augmented LAK cell activity in both a dose- and time-dependent manner. The augmentation was detected at 10(-10) M retinoic acid and reached the maximum at 10(-7) M, a greater than 200% increase in lytic activity. Kinetic study revealed that retinoic acid augmented significantly LAK cell activity when incubated in IL-2-containing culture as short as for 6 h before cytotoxicity was measured. The removal of retinoic acid from culture resulted in the loss of the augmentation. Retinoic acid was found to augment LAK cell activity in a wide range of IL-2 concentrations (750-12,000 IU/ml), even at 6,000 IU/ml where the maximal induction of LAK cell activity had been reached. No phenotype or proliferation of LAK cells was altered by the addition of retinoic acid to IL-2-containing culture. However, cellular serine protease activity, measured as N-alpha-benzyloxycarbonyl-L-lysine thiobenzyl-esterase, in LAK cells was increased by retinoic acid also in a dose- and time-dependent manner. The increase in LAK cellular serine protease activity was significantly correlated with that of augmented LAK cell activity. Overall these results demonstrated that IL-2-induced LAK cell activity was enhanced by retinoic acid and that the augmentation may be mediated by means of enhanced expression of cellular serine protease activity. This study also suggests that, in addition to its use in chemoprevention of cancer, retinoic acid is of potential in adoptive immunotherapy.

UI	MeSH Term	Description	Entries
D007111	Immunity, Cellular	Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.	Cell-Mediated Immunity,Cellular Immune Response,Cell Mediated Immunity,Cell-Mediated Immunities,Cellular Immune Responses,Cellular Immunities,Cellular Immunity,Immune Response, Cellular,Immune Responses, Cellular,Immunities, Cell-Mediated,Immunities, Cellular,Immunity, Cell-Mediated,Response, Cellular Immune
D007116	Immunization, Passive	Transfer of immunity from immunized to non-immune host by administration of serum antibodies, or transplantation of lymphocytes (ADOPTIVE TRANSFER).	Convalescent Plasma Therapy,Immunoglobulin Therapy,Immunotherapy, Passive,Normal Serum Globulin Therapy,Passive Antibody Transfer,Passive Transfer of Immunity,Serotherapy,Passive Immunotherapy,Therapy, Immunoglobulin,Antibody Transfer, Passive,Passive Immunization,Therapy, Convalescent Plasma,Transfer, Passive Antibody
D007376	Interleukin-2	A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.	IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D003602	Cytotoxicity, Immunologic	The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.	Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000945	Antigens, Differentiation, T-Lymphocyte	Antigens expressed on the cell membrane of T-lymphocytes during differentiation, activation, and normal and neoplastic transformation. Their phenotypic characterization is important in differential diagnosis and studies of thymic ontogeny and T-cell function.	Antigens, Differentiation, T-Cell,Differentiation Antigens, T-Cell,L3T4 Antigens,Leu Antigens, T-Lymphocyte,T-Cell Differentiation Antigens,T-Lymphocyte Differentiation Antigens,T6 Antigens,Antigens, Differentiation, T Lymphocyte,Differentiation Antigens, T Lymphocyte,Antigens, L3T4,Antigens, T-Cell Differentiation,Antigens, T-Lymphocyte Differentiation,Antigens, T-Lymphocyte Leu,Antigens, T6,Differentiation Antigens, T Cell,Differentiation Antigens, T-Lymphocyte,Leu Antigens, T Lymphocyte,T Cell Differentiation Antigens,T Lymphocyte Differentiation Antigens,T-Lymphocyte Leu Antigens
D000950	Antigens, Ly	A group of lymphocyte surface antigens located on mouse LYMPHOCYTES. Specific Ly antigens are useful markers for distinguishing subpopulations of lymphocytes.	Ly Antigens
D000954	Antigens, Surface	Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.	Cell Surface Antigens,Surface Antigens,Surface Markers, Immunological,Cell Surface Antigen,Immunologic Surface Markers,Markers, Immunological Surface,Surface Antigen,Surface Markers, Immunologic,Antigen, Cell Surface,Antigen, Surface,Antigens, Cell Surface,Immunological Surface Markers,Markers, Immunologic Surface,Surface Antigen, Cell,Surface Antigens, Cell