AlphaB-crystallin-reactive T cells from knockout mice are not encephalitogenic

Area of Science:

• Immunology
• Neuroscience
• Protein research

Background:

• Alpha B-crystallin (alphaB), a small heat shock protein, is upregulated in multiple sclerosis (MS) brain tissue.
• Assessing alphaB's encephalitogenic potential in MS and experimental autoimmune encephalomyelitis (EAE) is difficult due to its widespread expression, which typically induces tolerance.

Purpose of the Study:

• To investigate the encephalitogenic potential of alpha B-crystallin (alphaB) in the context of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE).
• To overcome immune tolerance to alphaB by using alphaB-knockout (alphaB-KO) mice.

Main Methods:

• Generated alphaB-knockout (alphaB-KO) mice to circumvent immune tolerance to alphaB protein.
• Immunized alphaB-KO mice with alphaB protein and generated alphaB-specific T cell lines.
• Transferred alphaB-reactive T cells into wild-type (WT) recipients and assessed for EAE induction.
• Compared EAE induction with MOG-35-55 peptide-reactive T cells.
• Evaluated the effect of alphaB-specific T cells on actively induced EAE in WT mice.

Main Results:

• T cell lines from alphaB-immunized alphaB-KO mice showed strong proliferation to alphaB and secreted pro-inflammatory Th1 cytokines.
• Transfer of alphaB-reactive T cells into WT recipients did not induce EAE.
• AlphaB-specific T cells did not augment the severity of actively induced EAE in WT mice.
• Control MOG-35-55 peptide-reactive T cells induced severe EAE in WT recipients.

Conclusions:

• Alpha B-crystallin (alphaB)-specific T cells are immunocompetent but not encephalitogenic in the studied mouse model.
• Immune tolerance may not be the primary factor limiting the encephalitogenic potential of alphaB in experimental autoimmune encephalomyelitis (EAE).