WC1+γδ; T cells indirectly regulate chemokine production during mycobacterium bovis Infection in SCID-bo mice

A. J. Alvarez, Janice Endsley, D. Werling, D. Mark Estes

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Summary Previous studies have suggested an important role for WC1 +γδ; T cells in the regulation of mycobacterial-induced inflammation in the spleen and liver of heterochimeric SCID-bovine (SCID-bo) mice. To examine the role of these cells, we investigated the levels of selected chemokines and IL12-p70 post-infection in reconstituted SCID-bo mice. Mice were treated with a monoclonal antibody specific for boWC1 to eliminate WC1-bearing cells. Isotype control treated or bovine γδ; TCR-depleted mice were assayed in parallel. Following infection with Mycobacterium bovis, mice were examined post-infection for the expression of IL12-p70, IP-10, MIP-1α, lymphotactin and MIG by ELISA in plasma and from activated splenocytes. Treatment with the anti-bovine WC1 resulted in reduced serum plasma levels of IP-10, MCP-1, and IL-12p70 versus control mice. The potential of WC1 +γδ; TCR-bearing cells to produce chemokines and cytokines was determined directly from peripheral blood of cattle. Our results indicate that these cells have a fairly restricted capability to produce the chemokines examined in SCID-bo mice, but may be a significant source of cytokines (IL-2, IL-10, IL-12, IL-15, and IFNγ) and contribute to cytotoxicity through expression of FasL and perforin. In M.bovis-infected liver tissue, depletion of the WC1+ subset was associated with increased numbers of CD3+T cells adjacent to venules and portal tracts. These results suggest that the WC1+ subset in cattle may contribute to chemotaxis through indirect effects on chemokine levels. Further, activated WC1+γδ; TCR+ cells up-regulate cytokines with direct regulatory effects on T cell and macrophage function and express effector molecules with critical roles in cytotoxicity.

Original languageEnglish (US)
Pages (from-to)275-284
Number of pages10
JournalTransboundary and Emerging Diseases
Volume56
Issue number6-7
DOIs
StatePublished - Aug 2009

Fingerprint

Mycobacterium Infections
SCID Mice
Mycobacterium bovis
chemokines
Chemokines
T-lymphocytes
T-Lymphocytes
Interleukin-12
mice
infection
Cytokines
cattle
cytokines
Infection
Interleukin-15
cells
Perforin
cytotoxicity
Venules
Liver

Keywords

  • Chemokines
  • Gamma delta T-cell receptor
  • Granuloma
  • Inflammation
  • Mycobacterium bovis
  • WC1

ASJC Scopus subject areas

  • veterinary(all)
  • Immunology and Microbiology(all)

Cite this

WC1+γδ; T cells indirectly regulate chemokine production during mycobacterium bovis Infection in SCID-bo mice. / Alvarez, A. J.; Endsley, Janice; Werling, D.; Mark Estes, D.

In: Transboundary and Emerging Diseases, Vol. 56, No. 6-7, 08.2009, p. 275-284.

Research output: Contribution to journalArticle

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abstract = "Summary Previous studies have suggested an important role for WC1 +γδ; T cells in the regulation of mycobacterial-induced inflammation in the spleen and liver of heterochimeric SCID-bovine (SCID-bo) mice. To examine the role of these cells, we investigated the levels of selected chemokines and IL12-p70 post-infection in reconstituted SCID-bo mice. Mice were treated with a monoclonal antibody specific for boWC1 to eliminate WC1-bearing cells. Isotype control treated or bovine γδ; TCR-depleted mice were assayed in parallel. Following infection with Mycobacterium bovis, mice were examined post-infection for the expression of IL12-p70, IP-10, MIP-1α, lymphotactin and MIG by ELISA in plasma and from activated splenocytes. Treatment with the anti-bovine WC1 resulted in reduced serum plasma levels of IP-10, MCP-1, and IL-12p70 versus control mice. The potential of WC1 +γδ; TCR-bearing cells to produce chemokines and cytokines was determined directly from peripheral blood of cattle. Our results indicate that these cells have a fairly restricted capability to produce the chemokines examined in SCID-bo mice, but may be a significant source of cytokines (IL-2, IL-10, IL-12, IL-15, and IFNγ) and contribute to cytotoxicity through expression of FasL and perforin. In M.bovis-infected liver tissue, depletion of the WC1+ subset was associated with increased numbers of CD3+T cells adjacent to venules and portal tracts. These results suggest that the WC1+ subset in cattle may contribute to chemotaxis through indirect effects on chemokine levels. Further, activated WC1+γδ; TCR+ cells up-regulate cytokines with direct regulatory effects on T cell and macrophage function and express effector molecules with critical roles in cytotoxicity.",
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