Related Experiment Videos
Recognition of Leishmania antigens by T lymphocytes from nonexposed individuals
M Kemp1, M B Hansen, T G Theander
1Department of Infectious Diseases 7641, University Hospital (Rigshospitalet), Denmark.
Insights
Even without known exposure, individuals possess circulating Leishmania-reactive T cells, primarily memory cells. These cells respond to Leishmania antigens, suggesting prior environmental encounters.
Area of Science:
- Immunology
- Parasitology
- Cellular Biology
Background:
- Leishmania parasites cause significant global health issues.
- Understanding immune responses in non-exposed individuals is crucial for vaccine development.
Purpose of the Study:
- To investigate the presence and characteristics of T cell responses to Leishmania antigens in individuals without known exposure.
- To identify the specific T cell subsets involved in these responses.
Main Methods:
- In vitro culture of peripheral blood mononuclear cells (PBMC) with Leishmania antigen preparations.
- Assessment of cell proliferation and gamma interferon production.
- Flow cytometry analysis, including cell depletion studies (CD45R0, CD45RA).
- Limiting dilution analysis to determine precursor cell frequencies.
Main Results:
- PBMC from unexposed individuals showed antigen-specific proliferation and gamma interferon production.
- Proliferation was primarily mediated by CD2-positive T cells and peaked after 6 days.
- Responses were abolished by CD45R0-positive (memory) cell depletion, but not CD45RA-positive (naive) cells.
- Antigen-reactive precursor cell frequencies were low (<1:10,000).
Conclusions:
- Presumably unexposed individuals harbor a low frequency of circulating Leishmania-reactive T cells.
- These reactive T cells are predominantly memory cells.
- The findings suggest prior, possibly environmental, exposure to antigens cross-reactive with Leishmania.
Abstract:
Crude antigen preparations of Leishmania promastigote sonicates were found to induce in vitro proliferation and gamma interferon production in peripheral blood mononuclear cells (PBMC) from individuals without known exposure to the parasite. The proliferating cells were mainly CD2-positive T cells. The proliferative response was maximal after more than 6 days of incubation with the antigens in contrast to the proliferation induced by the mitogenic lectin phytohemagglutinin (PHA), which peaked after 3 to 5 days. Judged by limiting dilution analysis, the frequencies of antigen-reactive precursor cells were less than 1:10,000 and varied considerably between individuals. Depletion of CD45R0-positive (memory) cells from the PBMC abolished proliferative responses induced by Leishmania antigen and by tetanus toxoid. In cell populations depleted of CD45RA-positive (naive) cells, only a small reduction in response was observed. Cell populations depleted of either CD45R0-positive cells or CD45RA-positive cells both responded to PHA. We conclude that presumably unexposed individuals have a low number of Leishmania-reactive T cells in their circulatory systems. The Leishmania-reactive T cells in these individuals are most likely memory cells recognizing antigens present both in the Leishmania preparations and in the environment.