Acquisition of functional MHC class II/peptide complexes by T cells during thymic development and CNS-directed...

Area of Science:

• Immunology
• Cell Biology

Background:

• T cells play a critical role in adaptive immunity.
• MHC class II glycoproteins (MHCII) are typically expressed on antigen-presenting cells (APCs).
• The expression and function of MHCII on T cells themselves are not fully understood.

Purpose of the Study:

• To investigate the in vivo expression and acquisition of MHCII on T cells in rats and mice.
• To determine the physiological relevance of MHCII expression on T cells in immune tolerance and inflammation.

Main Methods:

• Generation of rat and mouse chimeras to study MHCII acquisition.
• Analysis of MHCII expression on thymic and splenic T cells.
• Adoptive transfer experiments using T cells in models of experimental autoimmune encephalomyelitis (EAE) and tolerance induction.

Main Results:

• Both rat and mouse thymic and splenic T cells express significant levels of MHCII in vivo.
• Thymic T cells acquire MHCII primarily from radioresistant host APCs.
• MHCII expression on thymic T cells is functionally relevant for tolerance induction.
• Mature T cells from the central nervous system (CNS) in EAE models also express MHCII.
• Encephalitogenic T cells acquire allogeneic MHCII during inflammation.

Conclusions:

• Immature and mature T cells in rats and mice acquire functional MHCII in vivo.
• This acquisition occurs during thymic development and pathogenic inflammation.
• Acquired MHCII on T cells has implications for immune regulation and disease pathogenesis.