Spontaneous T cell apoptosis in feline immunodeficiency virus (FIV)-infected cats is inhibited by IL2 and anti-B7.1 antibodies.
Lymph node (LN) T cells from feline immunodeficiency virus (FIV)-infected cats have an increased expression of B7 co-stimulatory molecules as well as their ligand CTLA4, resembling an activation phenotype shown to induce anergy and apoptosis in activated T cells. In addition, LN T cells from FIV-infected cats also show increased spontaneous apoptosis compared to uninfected animals. The apoptosis observed in these animals occurs primarily in T cells expressing B7 and CTLA4, suggesting a role for B7 and CTLA4 interactions in the induction of anergy/apoptosis. In order to investigate the role of B7 and CTLA4 interactions on T cell apoptosis in LN T cells from FIV-infected cats, we performed blocking experiments by measuring T cell apoptosis in LN T cell cultures treated with anti-feline B7.1, B7.2, and CTLA4 specific antibodies, as well as interleukin (IL)-2. The addition of IL2, the primary cytokine produced by B7/CD28 interactions, resulted in a significant decrease of T cell apoptosis in cultured LN cells as assessed by two-color flow cytometry and TUNEL assay. The addition of anti-B7.1 antibodies significantly inhibited T cell apoptosis in FIV-infected cats with low-level plasma viremia, while addition of anti-B7.2 and anti-CTLA4 antibodies had no affect. These results suggest a role of B7 signaling in the increased spontaneous apoptosis observed in LN T cells from FIV-infected animals.
Bull
Marta E
ME
Immunology Program, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough St., Raleigh, NC 27606, USA.
Vahlenkamp
Thomas W
TW
Dow
Janet L
JL
Collisson
Ellen W
EW
Winslow
Barbara J
BJ
Phadke
Anagha P
AP
Tompkins
Mary B
MB
Tompkins
Wayne A F
WA
D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002415:Cats; D016181:Feline Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000276:immunology*; D020287:In Situ Nick-End Labeling / Q000662:veterinary; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013047:Specific Pathogen-Free Organisms
D019138:Antibodies, Blocking; D015703:Antigens, CD; D051940:B7-2 Antigen; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D012367:RNA, Viral