Feline immunodeficiency virus infection is characterized by B7+CTLA4+ T cell apoptosis.
The B7.1 and B7.2 costimulatory molecules on antigen-presenting cells provide second signals for regulating T cell immune responses via CD28 and cytotoxic T lymphocyte antigen 4 (CTLA4) on T cells. CD28 signals cell proliferation, whereas CTLA4 signals for anergy or apoptosis, terminating the immune response. Because T cell apoptosis and immunodeficiency is a characteristic of feline immunodeficiency virus (FIV)-infected cats, it is possible that negative T cell signaling via B7 and CTLA4 may be favored in these cats. Flow cytometry revealed high percentages of CD8+ and CD4+ cells expressing B7.1, B7.2, and CTLA4 in lymph nodes of FIV-positive cats and a large fraction of CTLA4+ T cells coexpressing B7.1 and B7.2. Three-color analysis with anti-B7.1, anti-B7.2, or anti-CTLA4 and TUNEL (terminal deoxynucleotidyl transferase nick-end-labeling) analysis revealed that apoptosis was a characteristic of B7.1+ B7.2+ CTLA4+ T cells. These data support the hypothesis that lymph node apoptosis and immune deterioration in FIV-infected cats results from chronic B7.1- and/or B7.2-CTLA4-mediated T-T interactions.
Tompkins
Mary B
MB
Department of Microbiology, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
Bull
Marta E
ME
Dow
Janet L
JL
Ball
Judith M
JM
Collisson
Ellen W
EW
Winslow
Barbara J
BJ
Phadke
Anagha P
AP
Vahlenkamp
Thomas W
TW
Tompkins
Wayne A
WA
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D000943:Antigens, Differentiation / Q000032:analysis*; D017209:Apoptosis; D018122:B7-1 Antigen / Q000032:analysis*; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D002415:Cats; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology*; D018796:Immunoconjugates; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000032:analysis*; D013601:T-Lymphocytes / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D000069594:Abatacept