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Functional involvement of the LFA-1/ICAM-1 adhesion system in the autologous mixed lymphocyte reaction
M Bagnasco1, G Pesce, C Prozato
1Istituto Scientifico di Medicina Interna, University of Genoa, Italy.
Insights
Monoclonal antibodies targeting lymphocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) inhibit T cell proliferation in autologous mixed lymphocyte reactions (AMLR). This suggests LFA-1 and ICAM-1 are crucial for T cell cooperation in AMLR.
Area of Science:
- Immunology
- Cell Biology
Background:
- Lymphocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) are critical for cell-to-cell contact in immune responses like MLR and cytotoxicity.
- Autologous mixed lymphocyte reaction (AMLR) models Ia-mediated immunocompetent cell cooperation and is often impaired in diseases.
Purpose of the Study:
- To investigate the role of LFA-1 and ICAM-1 in T cell proliferation within autologous mixed lymphocyte reactions (AMLR).
Main Methods:
- Utilized monoclonal antibodies (mAbs) against LFA-1 and ICAM-1 to assess their impact on T cell proliferation in AMLR.
- Examined the expression levels of LFA-1 on T cells and ICAM-1 on resting and stimulated T cells.
Main Results:
- Monoclonal antibodies targeting both LFA-1 and ICAM-1 significantly inhibited T cell proliferation in AMLR.
- LFA-1 is highly expressed on T cells, while ICAM-1 expression is low on resting T cells but increases upon autologous stimulation.
- Pretreatment experiments revealed that anti-ICAM-1 mAb's inhibitory effect on T cell proliferation in AMLR is mediated through responder T cells.
Conclusions:
- LFA-1 and ICAM-1 play a significant role in regulating T cell proliferation during autologous mixed lymphocyte reactions.
- Targeting ICAM-1, particularly on responder T cells, offers a potential strategy for modulating T cell cooperation in AMLR.
Abstract:
The integrin surface molecule termed lymphocyte functional antigen-1 (LFA-1), and its physiological ligand intercellular adhesion molecule-1 (ICAM-1), have been proven to play a relevant role in several immune reactions where cell-to-cell contact is required: these reactions include allogeneic mixed lymphocyte reaction (MLR) and direct cytotoxicity. In the present study, we show that monoclonal antibodies (mAbs) directed to LFA-1 as well as to ICAM-1 molecules are able to inhibit T cell proliferation in autologous MLR (AMLR). Such an in vitro reaction is generally considered a functional model of Ia-mediated immunocompetent cell cooperation, and is impaired in several pathological conditions. It is noteworthy that the LFA-1 molecule is largely represented on the T cell surface, whereas ICAM-1 is poorly expressed on resting T cells: autologous stimulation slightly increases ICAM-1 expression. Pretreatment studies indicate that the inhibitory effect of anti-ICAM-1 mAb on T cell proliferation in AMLR is exerted on responder T cells.