title: Peripheral T-lymphocyte activation by human T-cell leukemia virus type I interferes with the CD2 but not with the CD3/TCR pathway.
abstract: Human T-cell leukemia virus type I (HTLV-I) is etiologically associated with adult T-cell leukemia, an aggressive lymphoproliferative disorder, and with chronic neurological diseases. In vitro it can infect several types of cells but transforms only human T lymphocytes. We have previously shown that HTLV-I viral particles, even when noninfectious, were able to activate human resting T lymphocytes, suggesting that this activation step may be important in the initiation of the lymphoproliferative process. In the present study, we first demonstrate that in contrast to other mitogenic stimuli, HTLV-I has the unique property to activate human resting T cells in the absence of accessory cells. We then investigate the relationship between HTLV-I-induced T-cell activation and the classical well-known pathways of activation, namely, the CD3/TCR and CD2 pathways. Competitive blocking experiments were performed in which the effects of monoclonal antibodies (MAb) to the CD3/TCR complex or to the CD2 molecule were evaluated on the HTLV-I activation of T cells and compared with that obtained on phytohemagglutinin (PHA)-stimulated cells. It was found that anti-CD3 or -TCR MAb strongly suppress the proliferative response of T cells to PHA, but are significantly less efficient in inhibiting the activation initiated by HTLV-I. By contrast, MAb recognizing specific epitopes of the CD2 molecule inhibit the proliferative response of T cells to PHA or to HTLV-I to the same extent. The results provide evidence that HTLV-I virions interfere mainly with activation via CD2 but not via the CD3/TCR complex. Considering the earlier expression of the CD2 molecule on human T-cell precursors, these observations might be relevant to the characterization of the differentiation stage at which viral infection could interfere with the development and the maturation of T lymphocytes.
authors.affiliation: Immuno-Virologie Moléculaire et Cellulaire, UMR30 Centre National de la Recherche Scientifique-Université Claude Bernard, Lyon, France.
authors.forename: M D
authors.initials: MD
authors.lastname: Dodon
authors.forename: A
authors.initials: A
authors.lastname: Bernard
authors.forename: L
authors.initials: L
authors.lastname: Gazzolo
mesh_terms: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018801:CD2 Antigens; D017252:CD3 Complex; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014771:Virion / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic