Recovery of the T-cell repertoire in CIDP by IV immunoglobulins

Abstract

To investigate changes in the T-cell repertoire in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) without and with treatment of IV immunoglobulins (IVIg). The T-cell receptor (TCR) repertoire of CD4+ and CD8+ T cells in the peripheral blood was analyzed using CDR3 spectratyping. Patients with CIDP were included without (n = 14) and with IVIg treatment (n = 11) cross-sectionally and longitudinally (n = 2). While the TCR length distribution of patients with CIDP was only moderately altered for most of the Vβ elements of CD4+ T cells, the CD8+ population displayed extensive oligoclonal expansions in all analyzed 24 Vβ elements. A public expansion of a distinct TCR length in one Vβ element within a majority of affected patients was not detectable. Treatment with IVIg reduced the oligoclonal expansions within both the CD4+ and CD8+ population. Our data demonstrate that cytotoxic CD8+ T cells exhibit a much broader activation than CD4+ T cells, indicating a potentially crucial role of CD8+ T cells in the immunopathogenesis of CIDP. The profound oligoclonal response in T-cell activation suggests that multiple peptides may induce and propagate this autoimmune-driven disease. The observed reduction of highly activated T cells may contribute to the therapeutic effects of IVIg.