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Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
LFA-1-deficient mice show normal CTL responses to virus but fail to reject immunogenic tumor
R Schmits1, T M Kündig, D M Baker
1Amgen Institute, Ontario Cancer Institute, Department of Medical Biophysics, Toronto, Canada.
Insights
Mice lacking leukocyte function-associated antigen-1 (LFA-1) showed impaired peripheral immune responses, including tumor rejection. However, their ability to fight systemic viral infections remained normal, indicating a selective immune defect.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Medicine
Background:
- Leukocyte function-associated antigen-1 (LFA-1), also known as CD11a/CD18, is crucial for lymphocyte recirculation and cell-to-cell interactions.
- Integrins like LFA-1 mediate essential immune cell functions.
Purpose of the Study:
- To investigate the specific role of CD11a in immune responses, particularly in the context of viral infections and tumor immunity.
- To determine if CD11a deficiency impacts T cell responses to systemic infections versus peripheral immune challenges.
Main Methods:
- Analysis of CD11a-deficient mice.
- In vitro assays for homotypic aggregation and mitogen response.
- Assessment of cytotoxic T cell (CTL) responses to viral infections (LCMV, VSV).
- Evaluation of tumor rejection and immune priming against tumor-specific antigens in vivo.
Main Results:
- CD11a-deficient leukocytes exhibited defects in homotypic aggregation, mixed lymphocyte reactions, and mitogen responses.
- Mutant mice mounted effective CTL responses against systemic viral infections.
- LFA-1-deficient mice failed to reject immunogenic tumors and showed impaired priming to tumor antigens.
- CD11a deficiency resulted in a selective impairment of peripheral immune responses.
Conclusions:
- CD11a is essential for certain peripheral immune responses, such as tumor immunity and immune priming.
- The absence of CD11a does not compromise the ability to combat systemic viral infections, highlighting a selective role in adaptive immunity.
Abstract:
The leukocyte integrin LFA-1 (CD11a/CD18) plays an important role in lymphocyte recirculation and homotypic interactions. Leukocytes from mice lacking CD11a displayed defects in in vitro homotypic aggregation, in proliferation in mixed lymphocyte reactions, and in response to mitogen. Mutant mice mounted normal cytotoxic T cell (CTL) responses against systemic LCMV and VSV infections and showed normal ex vivo CTL function. However, LFA-1-deficient mice did not reject immunogenic tumors grafted into footpads and did not demonstrate priming response against tumor-specific antigen. Thus CD11a deficiency causes a selective defect in induction of peripheral immune responses whereas responses to systemic infection are normal.
