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Feline immunodeficiency virus infection phenotypically and functionally activates immunosuppressive CD4+CD25+ T

Thomas W Vahlenkamp1, Mary B Tompkins, Wayne A F Tompkins

  • 1Immunology Program, North Carolina State University, Raleigh, NC 27606, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|April 7, 2004
PubMed

Insights

Feline immunodeficiency virus (FIV) infection causes CD4(+) T cells to develop an immunosuppressive phenotype, similar to T regulatory (Treg) cells. These FIV-induced Treg-like cells may drive the immune dysfunction seen in FIV infection.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Feline immunodeficiency virus (FIV) infection is characterized by immune system decline.
  • Disease progression involves changes in T cell populations, including CD4(+) and CD8(+) T cells.
  • Up-regulation of B7.1, B7.2, and CTLA4 molecules is observed on T cells during FIV infection.

Purpose of the Study:

  • To investigate the phenotypic and functional characteristics of CD4(+)CD25(+) T cells in FIV-infected cats.
  • To compare these cells with T regulatory (Treg) cells.
  • To determine the role of these cells in FIV-induced immune dysfunction.

Main Methods:

  • Isolation and analysis of CD4(+)CD25(+) T cells from peripheral blood mononuclear cells (PBMC) and lymph nodes (LN) of FIV(+) and control cats.
  • Flow-cytometric analysis to assess cell surface marker expression (CD25, CTLA4, B7.1, B7.2).
  • Assays to measure IL-2 production and T cell proliferation in response to mitogen stimulation.

Main Results:

  • Feline CD4(+)CD25(+) T cells from LN of FIV(+) cats exhibited a lack of IL-2 production and failed to proliferate upon mitogen stimulation, similar to Treg cells.
  • Unstimulated CD4(+)CD25(+) T cells from FIV(+) cats significantly suppressed the proliferation and IL-2 production of autologous CD4(+)CD25(-) T cells.
  • Flow cytometry confirmed up-regulation of CD25, CTLA4, B7.1, and B7.2 on CD4(+) T cells in LN of chronically FIV(+) cats, indicating an activated, anergic phenotype.

Conclusions:

  • FIV infection induces CD4(+)CD25(+) T cells with an immunosuppressive, Treg-like phenotype.
  • These FIV-activated, anergic Treg-like cells express CTLA4 and B7 molecules.
  • These cells may contribute to the progressive loss of T cell immune function characteristic of FIV infection.

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