Feline Immunodeficiency Virus Infection Is Characterized by B7⁺CTLA4⁺T Cell Apoptosis

Abstract

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.

Preferential Feline Immunodeficiency Virus (FIV) Infection of CD4+CD25+T-Regulatory Cells Correlates both with Surface Expression of CXCR4 and Activation of FIV Long Terminal Repeat Binding Cellular Transcriptional Factors

“…Lymphocytes were obtained either from lymph nodes (LN) or whole blood. LN cells were obtained by peripheral LN biopsies as described previously (48). Peripheral blood mononuclear cells (PBMC) were isolated from whole blood by Percoll (Sigma, St. Louis, Mo.)…”

Generation of Feline Dendritic Cells Derived from Peripheral Blood Monocytes for In Vivo Use

“…Monoclonal antibodies used in this study were anti-CD14-phycoerythrin (TUK4), which cross-reacts with feline CD14 (1), and its negative isotypematched control (Serotec, Raleigh, NC), anti-feline CD1a (FE1.5F4) and MHC class II (42.3), provided by Peter F. Moore, University of California, Davis. Anti-feline B7.1 (B7.1.66) was a kind gift from Wayne Tompkins, North Carolina State University (25). The negative control for all unlabeled immunoglobulin G1 (IgG1) isotype antibodies was monoclonal antibody L8D8 (6).…”

Puma Lentivirus Is Controlled in Domestic Cats after Mucosal Exposure in the Absence of Conventional Indicators of Immunity

“…A greater level of apoptosis compared to controls has been documented in lymph nodes of FIV-infected animals (47), and altered cytokine expression (2,3,17,33,34) and an increased activation state of FIV-infected cells have been reported (46). However, one report of increased immune activation in FIVinfected cats by exposure to other viral and bacterial pathogens did not result in accelerated CD4 ϩ lymphocyte loss (44).…”