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Immune responsiveness in mutant mice lacking T-cell receptor alpha beta+ cells
P Chandler1, A J Frater, D C Douek
1MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Immunology
|August 1, 1995
Summary
Mice lacking T-cell receptor alpha beta+ cells show compromised immune responses to certain antigens. However, their gamma delta T cells can still reject skin grafts mismatched for non-classical MHC antigens, suggesting a role for these cells and antigens in immune responses.
Area of Science:
- Immunology
- T-cell biology
- Transplantation immunology
Background:
- T-cell receptor (TCR) alpha beta+ and gamma delta+ T cells mediate distinct immune functions.
- TCR alpha-/- mice lack TCR alpha beta+ T cells, relying primarily on gamma delta+ T cells for adaptive immunity.
- The role of gamma delta T cells in responses to alloantigens and Mycobacterium tuberculosis is not fully understood.
Purpose of the Study:
- To analyze the immune responses of TCR alpha-/- mice against various antigens.
- To investigate the role of gamma delta T cells in allograft rejection and responses to Mycobacterium tuberculosis.
- To determine the significance of non-classical MHC antigens in immune recognition by TCR alpha-/- mice.
Main Methods:
- Immune response analysis in TCR alpha-/- mice against alloantigens, soluble protein antigen, killed Mycobacterium tuberculosis, and superantigen.
- Skin allograft rejection studies using donor tissue mismatched for classical MHC, minor H antigens, and non-classical Qa-1 antigens.
- Assessment of local and splenic T cell responses to Mycobacterium tuberculosis components, including HSP 65 and PPD.
Main Results:
- Rejection of skin allografts mismatched for classical MHC and minor H antigens was abrogated in TCR alpha-/- mice.
- A significant proportion of TCR alpha-/- mice rejected allografts mismatched for non-classical Qa-1 antigens.
- Splenic T cells from TCR alpha-/- mice responded strongly to PPD and M. tuberculosis, but not to mycobacterial HSP 65.
- Responses to MHC alloantigens were poor or absent, despite substantial responses to mycobacterial antigens.
Conclusions:
- TCR alpha-/- mice exhibit selective immune deficiencies, with impaired responses to certain alloantigens and HSP 65.
- Gamma delta T cells in TCR alpha-/- mice can mediate skin graft rejection, particularly when non-classical MHC antigens (Qa-1) are involved.
- Recognition of non-classical MHC antigens may play a crucial role in immune responses mediated by residual gamma delta T cells.