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

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-137 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. (C) 2004 Elsevier B.V. All rights reserved.