Cellular Immune Response

Marinos C. Dalakas, M.D., Principal Author

In autoimmune diseases, such as CIDP, autoreactive T and B cells are unleashed, become activated, and cause organ-specific damage. (Kieseier, 2002; Quattrini, 2003) Evidence of T-cell activation in the systemic immune compartment in patients with CIDP exists, although antigen specificity remains largely unknown. (Hartung, 1991; Dalakas, 1999; Van den Berg, 1995) Activated T cells cross the blood-nerve barrier (BNB) of patients with CIDP. As a result, these patients have increased levels of soluble adhesion molecules, chemokines, and matrix metalloproteinases in serum, in cerebral spinal fluid (CSF), or in both. (Keiseier, 2002; Previtali, 1998; Previtali, 2001; Kastenbauer, 2003; Leppert, 1999; Keiseier, 1998)

The activated T cells, once they have entered the PNS, may undergo clonal expansion following an encounter with an antigen presented in the context of appropriate major-histocompatability-complex molecules and co-stimulatory signals expressed on the macrophages and the Schwann cells. (Köller, 2005; Murata, 2000)

Activated T cells express and secrete cytokines, including tumor necrosis factor (TNF), alpha and interferon-γ, and interleukin-2. (Gold, 1999; Mathey, 1999). T cells then activate resident endoneurial macrophages, which secrete several neurotoxic and immunopotentiating molecules, such as oxygen radicals, nitric oxide metabolites, proteases, and complement components. (Keifer, 2001; Hu, 2003). T cells also engage in increased phagocytic and cytotoxic activity against myelin or Schwann cells.

Specialized subpopulations of T cells may terminate the acute immunoinflammatory process by secreting down-regulatory cytokines (e.g., transforming growth factor β;) or other molecules. (Köller, 2005) Macrophages may also serve as antigen-presenting cells in CIDP, a finding that is made evident by the observed expression of the major-histocompatability-complex class II molecule CD1a in nerve-biopsy specimens. (Van Rhijn, 2000)

Co-stimulatory. molecules B7-1 and B7-2, which are essential for effective antigen presentation, may determine the differentiation of T lymphocytes into a phenotype of type 1 or type 2 helper cells. (Köller, 2005) These molecules are expressed on endoneurial macrophages and Schwann cells, both of which may serve as antigen presenting cells in CIDP.

The cellular immune response within the PNS is tightly regulated at the transcriptional level. One of its key regulators is the transcription factor nuclear factor-κβ which is up-regulated predominantly within the endoneurial macrophages in CIDP. (Köller, 2005)