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Published on: November 22, 2011
Lymphocytes bearing the gamma delta T cell receptor in acute Brucella melitensis infection
A Bertotto1, R Gerli, F Spinozzi
1Department of Pediatrics, Perugia University Medical School, Italy.
Insights
Brucella melitensis infection significantly increases gamma delta T cells in children. While both alpha beta and gamma delta T cells proliferate with mitogens, only alpha beta T cells respond to Brucella antigens, suggesting a complex immune response.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Brucella melitensis is a pathogen causing brucellosis.
- T cell receptor (TcR) gamma delta lymphocytes play a role in immune responses.
- The specific role of gamma delta T cells in Brucella infections is not fully understood.
Purpose of the Study:
- To investigate the phenotypical and functional characteristics of T cell subpopulations during Brucella melitensis infection.
- To determine the in vivo expansion and in vitro proliferative capacity of gamma delta T cells in response to Brucella antigens.
Main Methods:
- Indirect immunofluorescence and two-color cytofluorometry were used for phenotypical analysis.
- Negative immunoselection was employed to isolate alpha beta and gamma delta T cell populations.
- T cell proliferation assays were conducted using mitogenic anti-CD3 (OKT3) and heat-killed Brucella.
Main Results:
- A dramatic increase in gamma delta T cells bearing the gamma delta T cell receptor (TcR) was observed in children with Brucella melitensis infection.
- Expanded gamma delta T cells expressed V delta 2, CD25, and HLA-DR, indicating activation.
- While both T cell subsets proliferated to mitogens, only alpha beta T cells responded to heat-killed Brucella antigens.
Conclusions:
- Brucella infection leads to a significant in vivo expansion of activated gamma delta T cells.
- Gamma delta T cells do not proliferate in response to direct Brucella antigenic stimulation.
- Further research is needed to elucidate whether pathogen-derived or host-derived stimuli drive gamma delta T cell expansion during brucellosis.
Abstract:
A phenotypical analysis carried out by indirect immunofluorescence and two-color cytofluorometry showed that the number of lymphocytes bearing the gamma delta T cell receptor (TcR) heterodimer was dramatically increased in the blood of six children with Brucella melitensis infection. Most in vivo expanded gamma delta T cells reacted with a monoclonal antibody which identifies V delta 2 gene products and a significant proportion expressed CD25 and HLA-DR activation antigens. In addition, whereas only a few gamma delta T lymphocytes were CD8+, nearly all were CD4-. Highly enriched populations of both alpha beta and gamma delta T cells were obtained by negative immunoselection from three subjects with brucellosis sampled during convalescence. Despite the different form of their TcR, the proliferation of these two major T cell subsets in response to a mitogenic anti-CD3 monoclonal reagent (OKT3) was optimal. In contrast, alpha beta, but not gamma delta, T lymphocytes proliferated vigorously in response to the antigenic stimulus elicited by heat-killed Brucella. Further studies are, therefore, needed to determine whether the selective expansion of the gamma delta T cell subpopulation observed during the clinical course of the infection is driven by antigenic determinant(s) borne by the pathogen in vivo or is due to host-derived stimuli, such as autologous heat-shock proteins expressed on the surface of the infected cells.
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