The effect of partial in vivo depletion of CD4 T cells by monoclonal antibody. Evidence that incomplete depletion increases IgG production and augments in vitro thymic-dependent antibody responses.
In vivo depletion or inactivation of CD4 T cells by monoclonal antibody inhibits of T-cell-dependent immune responses and, in some cases, ameliorates clinical autoimmune disease. Impairment of T cell function occurs in situations where mice are treated with relatively large doses of anti-CD4 antibody. When adult (C57BL/6xDBA/2)F1 mice were treated with a low dose of anti-CD4 antibody augmentation of certain thymic-dependent responses occurred. Twice-weekly injections of 50 micrograms of monoclonal antibody GK1.5 for a period of three weeks resulted in a 50% reduction of splenic CD4 T cells. Mice that were partially depleted of CD4 T cells exhibited a 55% increase in serum IgG levels with a 165% increase in serum IgG1. Simulation of spleen cells from these mice with LPS resulted in a significant increase in differentiation of IgG secretion. When spleen cells from partially CD4-depleted mice were challenged in vitro with SRBC, they mounted a direct PFC response that was more than four times the observed PFC response of mice that received either saline or rat IgG. These findings indicate that partial depletion/inactivation of CD4 T cells by in vivo administration of anti-CD4 monoclonal antibody results in a significant augmentation of certain T-cell-dependent humoral responses.
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
J S
JS
Cowdery
N
N
Tolaymat
S P
SP
Weber
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000917:Antibody Formation; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008212:Lymphocyte Depletion; D051379:Mice; D008815:Mice, Inbred Strains; D013950:Thymus Gland / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007074:Immunoglobulin G