Dissecting memory T cell responses to TB: concerns using adoptive transfer into immunodeficient mice

Area of Science:

• Immunology
• T cell biology
• Infectious disease research

Background:

• Previous studies identified CD62L(hi) memory CD4(+) T cells from BCG-vaccinated mice as crucial for tuberculosis protection.
• Adoptive transfer into immunodeficient mice is a common model to study T cell-mediated immunity against Mycobacterium tuberculosis.

Purpose of the Study:

• To investigate the protective capacity of different CD4(+) T cell subsets against Mycobacterium tuberculosis.
• To evaluate the safety and validity of using adoptive T cell transfer models in immunodeficient mice for tuberculosis research.

Main Methods:

• Purified naïve and BCG-experienced CD4(+) T cell subsets were adoptively transferred into Rag1-/- immunodeficient mice.
• Mice were challenged with Mycobacterium tuberculosis, and protection was assessed.
• Colitis induction and T cell proliferation/phenotype in the lung were monitored post-transfer.

Main Results:

• Transfer of naïve CD4(+) T cells conferred protection comparable to BCG-experienced T cells.
• Both naïve and CD62L(hi)CD4(+) T cells from vaccinated mice induced severe colitis.
• CD62L(lo)CD4(+) T cells from vaccinated mice did not induce colitis.
• Transferred naïve and CD62L(hi)CD4(+) T cells showed extensive proliferation and activation in the lung, independent of infection.

Conclusions:

• The adoptive transfer model using immunodeficient mice may be compromised by T cell-induced colitis and systemic inflammation.
• The observed T cell activation and colitis raise concerns about the model's ability to accurately assess CD4(+) T cell-mediated protection against tuberculosis.
• Further refinement of animal models is needed to reliably study T cell responses in tuberculosis.