Kinetics of W3/25 anti-rat CD4 monoclonal antibody. Studies on optimal doses and time-related effects. 1998

F Caballero, and C Pelegrí, and M Castell, and A Franch, and C Castellote
Unit of Physiology, Faculty of Pharmacy, University of Barcelona, Spain.

Although anti-CD4 monoclonal antibodies (MoAb) have been proven successful in preventing or treating adjuvant arthritis, little is known about the duration of the effects of these MoAb and their pharmacokinetics. In this work, we report the effects of a mouse anti-rat CD4 MoAb, named W3/25, on peripheral blood lymphocytes from female Wistar rats. Animals received a single dose of W3/25, from 1 to 3 mg, and blood was sampled at different time points from 0 h to 15 days after MoAb administration. After erythrocyte lysis, samples were stained by indirect immunofluorescence and analyzed by flow cytometry. Pharmacokinetic data were studied by assessing plasma levels of mouse IgG1 by ELISA-sandwich. W3/25 produced the down-regulation of surface CD4 molecule as early as 20 min after its administration at doses of 2 and 3 mg. The same effect was seen 30 min after a dose of 1 mg. The recovery of lymphocytes with normal expression of CD4 also depended of the dose administered. Thus, CD4+ lymphocytes were recovered at 48, 72 and 96 h in rats treated with 1, 2 or 3 mg of W3/25, respectively. Plasma levels of free antibody were detectable from 20 min to 72 h, 60 min to 48 h and 60 min to 24 h after administration of 3, 2 and 1 mg, respectively, of W3/25. The mouse IgG1 MoAb used in this study followed a two-compartment model and its behavior was linear.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007700 Kinetics The rate dynamics in chemical or physical systems.
D004306 Dose-Response Relationship, Immunologic A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell. Immunologic Dose-Response Relationship,Relationship, Immunologic Dose-Response,Dose Response Relationship, Immunologic,Dose-Response Relationships, Immunologic,Immunologic Dose Response Relationship,Immunologic Dose-Response Relationships,Relationship, Immunologic Dose Response,Relationships, Immunologic Dose-Response
D005260 Female Females
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
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D015704 CD4 Antigens 55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. They are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. T4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120. Antigens, CD4,CD4 Molecule,CD4 Receptor,CD4 Receptors,Receptors, CD4,T4 Antigens, T-Cell,CD4 Antigen,Receptors, Surface CD4,Surface CD4 Receptor,Antigen, CD4,Antigens, T-Cell T4,CD4 Receptor, Surface,CD4 Receptors, Surface,Receptor, CD4,Surface CD4 Receptors,T-Cell T4 Antigens,T4 Antigens, T Cell
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

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