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Beta chemokines costimulate lymphocyte cytolysis, proliferation, and lymphokine production. 1996

D D Taub, and J R Ortaldo, and S M Turcovski-Corrales, and M L Key, and D L Longo, and W J Murphy
Clinical Services Program, SAIC-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA.

We report here the ability of the beta chemokines MIP-1 alpha, MIP-1 beta, RANTES, and MCP-1 to enhance some lymphocyte effector functions. Initial studies focused on the effects of chemokines on human and mouse cytotoxic T lymphocyte (CTL)- and natural killer (NK) cell-specific cytolytic responses. The results demonstrate that beta chemokines are capable of augmenting mouse and human CTL and human NK- but not lymphokine-activated killer cell- or antibody-dependent cell cytotoxicity-specific cytolytic responses. Neutralization analysis utilizing integrin-specific antibodies revealed that CTL/NK tumor cell conjugate formation is required for chemokine-induced killing. In addition, both CTLs and NK cells incubated with various beta chemokines were induced to degranulate and release granule-derived serine esterases, suggesting that chemokines may be important costimulators of CTL and NK cell degranulation and may thus augment local target cell destruction. Chemokines also modulate antigen-driven T cell proliferative responses as well as effects on lymphokine production. Many of the beta chemokines were found to potentiate human and mouse antigen-specific Th1 and Th2 clone activation promoting cellular proliferation and the release of various lymphokines. This chemokine-mediated T cell proliferation was chemokine and antigen dose dependent as well as clone dependent. Chemokine pretreatment analyses with T cells and antigen-presenting cells (APCs) revealed that chemokines up-regulate both T cells and antigen- presenting cells (APCs) revealed that chemokines up-regulate both T cell and APC functions. Costimulation assays using immobilized antiCD3 monoclonal antibody-coated plates and purified human and mouse T cells and T cell clones in the presence of various chemokines also exhibited enhanced proliferation and lymphokine secretion. This costimulation was interleukin-2 dependent and required the presence of free extracellular calcium. Examination of chemokine-treated APCs revealed that the T cell costimulatory molecule B7-1 was induced by various beta chemokines. Neutralization of endogenously produced chemokines, with specific antibodies during an antigen-specific T cell response blocked cellular proliferation, suggesting that the chemokines have an autocrine role in antigen-induced T cell proliferative responses. Together, these results suggest that chemokines play a significant role in the activation of polyclonal as well as antigen-specific helper and cytotoxic T cells during the genesis of an immune response.

UI MeSH Term Description Entries
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008222 Lymphokines Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. Lymphocyte Mediators,Mediators, Lymphocyte
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
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D000938 Antigen-Presenting Cells A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors. Accessory Cells, Immunologic,Antigen-Presenting Cell,Immunologic Accessory Cells,Accessory Cell, Immunologic,Cell, Immunologic Accessory,Cells, Immunologic Accessory,Immunologic Accessory Cell,Antigen Presenting Cell,Antigen Presenting Cells,Cell, Antigen-Presenting,Cells, Antigen-Presenting
D013268 Stimulation, Chemical The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Stimulation,Chemical Stimulations,Stimulations, Chemical
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018925 Chemokines Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif. Chemokine,Chemotactic Cytokine,Chemotactic Cytokines,Cytokines, Chemotactic,Intercrine,Intercrines,Cytokine, Chemotactic

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