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TB: epidemiology and diagnosis
S3 T Cell Responses to Vitamin D Are Blunted in Latent Tuberculosis
  1. G Hawthorne1,
  2. J Zhang1,
  3. L Jeffery2,
  4. D Thickett1,
  5. A Turner1
  1. 1School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK
  2. 2Medical Research Council Centre for Immune Regulation, School of Immunity and Infection, Institute of Biomedical Research, University of Birmingham Medical School, Birmingham, UK

Abstract

Introduction Low vitamin D status is associated with an increased risk of Mycobacterium Tuberculosis. Consistent with this, the active form of vitamin D, 1,25(OH)2D3 exerts potent effects on immune cells.

T cells are thought to contribute to the control of latent tuberculosis in which patients are infected with Mycobacterium tuberculosis but show no signs or symptoms of the disease. How vitamin D influences T cell responses in latent patients is therefore of interest.

It has been shown that the co-suppressive protein, CTLA4, which is expressed on regulatory T cells and induced in T cells upon activation, is strongly up regulated by vitamin D and that it increases the frequency of CTLA-4+FoxP3+ cells [1]. Furthermore, vitamin D conditioned T cells are functionally suppressive. In this study we have therefore compared the effect of vitamin D upon CTLA-4 expression and the frequency of CD25+ FoxP3+ CTLA4+ cells in healthy and latent TB patients.

Methods Peripheral blood cells from healthy control donors (n=21) and patients with latent tuberculosis (n=12) were cultured with SEB or PPD with or without 1,25(OH)2D3 or inactive 25(OH)D3. CD25+ FoxP3+ CTLA4+ frequency and the median CTLA-4 expression (MFI) of CD25+ cells was then monitored after two days by flow cytometry.

Results 1,25(OH)2D3 significantly increased CTLA4 MFI in both healthy and latent populations following stimulation with SEB (p≤0.01) or PPD (P=0.026, 0008). 25(OH)D3 also enhanced CTLA-4 expression in SEB cultures (p≤0.01). Induction of CTLA-4 was however reduced in PPD cultures (median 121) compared to SEB (median 360). Interestingly, the magnitude of CTLA-4 induction by 1,25(OH)2D3 or 25(OH)D3 also differed for healthy and latent populations in response to SEB (1,25(OH)2D3 (p=0.01) and 25(OH)D3 (p=0.006), with a similar trend in PPD stimulated cells (p=0. 092).

Conclusion The shift towards a T reg population as a result of vitamin D is blunted in latent TB compared to health. Differential response of memory cells in latent disease could account for this.

  1. Jeffery, LE, et al., 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. Journal of immunology, 2009. 183(9): p. 5458–67.

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