B7 +CTLA4 + T cells engage in T–T cell interactions that mediate apoptosis: a model for lentivirus-induced T cell depletion

• Published in: Veterinary immunology and immunopathology 2004-04, Vol.98 (3), p.203-214
• Main Authors: Vahlenkamp, Thomas W., Bull, Marta E., Dow, Janet L., Collisson, Ellen W., Winslow, Barbara J., Phadke, Anagha P., Tompkins, Wayne A.F., Tompkins, Mary B.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - biosynthesis; Antigens, CD - immunology; Antigens, Differentiation - biosynthesis; Antigens, Differentiation - immunology; Apoptosis; Apoptosis - immunology; B7 costimulatory molecules; B7-1 Antigen - biosynthesis; B7-1 Antigen - immunology; B7-2 Antigen; Cats; Cell Communication - immunology; Concanavalin A - immunology; CTLA-4 Antigen; CTLA4; Feline Acquired Immunodeficiency Syndrome - immunology; FIV; Flow Cytometry - veterinary; Immunodeficiency Virus, Feline - immunology; In Situ Nick-End Labeling - veterinary; Ionomycin - immunology; Lymphocyte Activation - immunology; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - immunology; Specific Pathogen-Free Organisms; T-Lymphocytes - immunology; T-Lymphocytes - virology; Tetradecanoylphorbol Acetate - immunology
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2003.12.006

Apoptosis in lymph node (LN) T cells of feline immunodeficiency virus (FIV)-infected cats is associated with cells co-expressing B7.1 and B7.2 costimulatory molecules, and their ligand CTLA4. To study the possibility of B7.1/B7.2–CTLA4 mediated T–T interactions and the predicted induction of T cell apoptosis in vitro, costimulatory molecules were up-regulated on CD4 + and CD8 + T cells by mitogen stimulation. B7.1 expression on in vitro stimulated CD4 + and CD8 + cells increased within 24 h; B7.2 and CTLA4 expression increased after 48–72 h. Apoptosis, as analyzed by terminal deoxynucleotidyl transferase (transferase nick end labeling, TUNEL)-based staining followed by three color flow cytometric analysis, correlated to the cells expressing B7 and/or CTLA4. Blocking experiments revealed that CD4 + and CD8 + T cell apoptosis could be significantly inhibited with anti-B7 antibodies. As FIV infection results in immune activation with a T cell phenotype similar to that of the in vitro activated T cells, the data support the hypothesis that the chronic expansion of B7 +CTLA4 + LN T cells in infected cats allows for T–T cell interactions resulting in T cell depletion and eventually the development of AIDS.