Effect of recombinant soluble CD4 on human peripheral blood lymphocyte responses in vitro. 1988

M A Liu, and T Liu
Endocrine Unit, Massachusetts General Hospital, Boston.

We have previously demonstrated that recombinant soluble CD4 protein (rsT4) blocks both HIV-1 infection of CD4 bearing lymphocytes and syncytium formation in vitro. (Recombinant soluble CD4 is designated by rsT4). Hence, we suggested the use of rsT4 in therapy for AIDS or the prevention of HIV-1 infection in individuals with a known risk of exposure. However, concerns arose that rsT4 might be immunosuppressive because of its implicated role in the enhancement of certain lymphocyte activation events through its engagement of MHC class II molecules on target cells. We therefore assessed the effect of recombinant soluble CD4 upon a number of functional and activation parameters of lymphocytes, including cellular proliferation, IL-2 secretion, and cytolytic capability, after antigenic or mitogenic stimulation. We report here that rsT4, at 60-fold over the concentration needed to block acute HIV-1 infection in vitro, does not significantly inhibit the activation of human peripheral blood lymphocytes by either PHA, tetanus toxoid or allogeneic cells. These results indicate that rsT4 will potentially exert minimal immunosuppressive effects in vivo, thus supporting the feasibility of clinical trials of rsT4 in the treatment or prevention of AIDS. In addition, the implications of these results for the interactions between CD4 and MHC class II molecules during lymphocyte activation are discussed.

UI MeSH Term Description Entries
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
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
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
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

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