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 24h; 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.
Vahlenkamp
Thomas W
TW
Immunology Program, North Carolina State University, Raleigh, NC 27606, USA. thomas_vahlenkamp@ncsu.edu
Bull
Marta E
ME
Dow
Janet L
JL
Collisson
Ellen W
EW
Winslow
Barbara J
BJ
Phadke
Anagha P
AP
Tompkins
Wayne A F
WA
Tompkins
Mary B
MB
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D002415:Cats; D002450:Cell Communication / Q000276:immunology; D003208:Concanavalin A / Q000276:immunology; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology*; D005434:Flow Cytometry / Q000662:veterinary; D016089:Immunodeficiency Virus, Feline / Q000276:immunology*; D020287:In Situ Nick-End Labeling / Q000662:veterinary; D015759:Ionomycin / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D008562:Membrane Glycoproteins; D003208:Concanavalin A; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate