Mycobacterium bovis bacille Calmette-Guerin vaccination of cattle: activation of bovine CD4+ and gamma delta TCR+ cells and modulation by 1,25-dihydroxyvitamin D3

Tuberculosis (Edinb). 2003;83(5):287-97. doi: 10.1016/s1472-9792(03)00002-7.

Abstract

Setting: 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3)) is a potent modulator of immune responses and may be beneficial in the treatment of tuberculosis. Recent evidence suggest that 1,25(OH)(2)D(3) may affect T-dependent responses in cattle; however, mechanisms by which this vitamin modulates activation of bovine T cells are unclear.

Objective: Determine the effects of 1,25(OH)(2)D(3) on the expression of CD25, CD44, and CD62L by bovine T cell subsets proliferating in response to antigen stimulation.

Design: Antigen-specific recall responses of Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccinated cattle were used as a model system to evaluate effects of 1,25(OH)(2)D(3) on the proliferation and activation of bovine T cell subsets.

Results: CD4(+) and gamma delta TCR(+) cells were the predominant T cell subsets responding to soluble crude M. bovis-derived antigens (i.e., purified protein derivative and a BCG whole cell sonicate) by proliferation and activation-induced alterations in phenotype. These subsets exhibited increased CD25 and CD44 mean fluorescence intensity (mfi) and decreased CD62L mfi upon antigen stimulation. Addition of 1,25(OH)(2)D(3) inhibited proliferation of CD4(+) cells and decreased the expression of CD44 on responding (i.e., proliferating) CD4(+) and gamma delta TCR(+) cells.

Conclusion: These findings suggest that the production of 1,25(OH)(2)D(3) by macrophages within tuberculous lesions would inhibit proliferation and CD44 expression by co-localized CD4(+) and gamma delta TCR(+) cells.

MeSH terms

  • Animals
  • BCG Vaccine / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Calcitriol / pharmacology*
  • Cattle
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Hyaluronan Receptors / metabolism
  • L-Selectin / metabolism
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Receptors, Interleukin-2 / metabolism
  • Tuberculosis, Bovine / immunology*
  • Vaccination

Substances

  • BCG Vaccine
  • Hyaluronan Receptors
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin-2
  • L-Selectin
  • Calcitriol