title: The quality of chimpanzee T-cell activation and simian immunodeficiency virus/human immunodeficiency virus susceptibility achieved via antibody-mediated T-cell receptor/CD3 stimulation is a function of the anti-CD3 antibody isotype.
abstract: While human immunodeficiency virus type 1 (HIV-1) infection is associated with hyperimmune activation and systemic depletion of CD4(+) T cells, simian immunodeficiency virus (SIV) infection in sooty mangabeys or chimpanzees does not exhibit these hallmarks. Control of immune activation is thought to be one of the major components that govern species-dependent differences in the disease pathogenesis. A previous study introduced the idea that the resistance of chimpanzees to SIVcpz infection-induced hyperimmune activation could be the result of the expression of select sialic acid-recognizing immunoglobulin (Ig)-like lectin (Siglec) superfamily members by chimpanzee T cells. Siglecs, which are absent on human T cells, were thought to control levels of T-cell activation in chimpanzees and were thus suggested as a cause for the pathogenic differences in the course of SIVcpz or HIV-1 infection. As in human models of T-cell activation, stimulation had been attempted using an anti-CD3 monoclonal antibody (MAb) (UCHT1; isotype IgG1), but despite efficient binding, UCHT1 failed to activate chimpanzee T cells, an activation block that could be partially overcome by MAb-induced Siglec-5 internalization. We herein demonstrate that anti-CD3 MAb-mediated chimpanzee T-cell activation is a function of the anti-CD3 MAb isotype and is not governed by Siglec expression. While IgG1 anti-CD3 MAbs fail to stimulate chimpanzee T cells, IgG2a anti-CD3 MAbs activate chimpanzee T cells in the absence of Siglec manipulations. Our results thus imply that prior to studying possible differences between human and chimpanzee T-cell activation, a relevant model of chimpanzee T cell activation needs to be established.
authors.affiliation: Division of Infectious Diseases, University of Alabama at Birmingham, BBRB 510, 845 19th Street, South Birmingham, AL 35294, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Bibollet-Ruche
authors.forename: Brett A
authors.initials: BA
authors.lastname: McKinney
authors.forename: Alexandra
authors.initials: A
authors.lastname: Duverger
authors.forename: Frederic H
authors.initials: FH
authors.lastname: Wagner
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Olaf
authors.initials: O
authors.lastname: Kutsch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology / Q000821:virology; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D002679:Pan troglodytes / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016415:Sequence Alignment; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D037102:Lectins; D011948:Receptors, Antigen, T-Cell; D063265:Sialic Acid Binding Immunoglobulin-like Lectins