Oligoclonal accumulation of T cells in peripheral blood from patients with idiopathic thrombocytopenic purpura

Abstract

To determine whether clonal T cells accumulate in idiopathic thrombocytopenic purpura (ITP), we performed single-strand conformation polymorphism (SSCP) analysis to detect T-cell receptor (TCR) beta-chain usage of peripheral T cells. We detected significantly more oligoclonal T cells (15.5 +/- 8.9 bands representative for clonal T-cell expansions) in peripheral blood from ITP patients than from healthy donors (2.8 +/- 2.6 bands). Frequently used V beta genes in these accumulated T cells in ITP were V beta 3, 6, 10, 13.1 and 14. To determine whether these bands were derived from clonal T cells, presumably in a preactivated state, we established some T-cell clones (expressing CD4 and TCR V beta 6. 13.1. or 14) by nonspecific stimulation from patients peripheral mononuclear cells, and examined their clonotypes. Clonal identities for three out of seven clones tested were confirmed using SSCP analyses to compare the migration of their beta-chain complementarity determining region 3 (CDR3) cDNAs, expanded by polymerase chain reaction (PCR) with those from peripheral blood. Therefore, distinctive T-cell clones accumulated in the periphery in ITP and they may be related to the autoimmune-mediated destruction of platelets.

Mapping helper T-cell epitopes on platelet membrane glycoprotein IIIa in chronic autoimmune thrombocytopenic purpura

“…Autoreactive Th cells specific for platelet glycoprotein are known to be activated in AITP, [11][12][13][14][15][16][17][18][19] but this is the first time that peptides driving the response have been mapped. The results not only provide further insight into the mechanisms of disease but open the way for novel forms of peptide immunotherapy [23][24][25][26][27] for AITP that selectively target the pathogenic Th cells.…”

“…11,12 Human AITP is no exception, because the disease is associated with loss of peripheral T-cell tolerance and the development of recall helper responses to platelet autoantigens. [13][14][15][16][17] Peripheral blood Th cells from patients with AITP, in comparison with those from healthy controls, exhibit accelerated proliferation when stimulated in vitro with fragments of purified 17 or recombinant 18 GPIIb/IIIa, indicative of prior activation in vivo. These memory Th cells are capable of driving anti-GPIIb/IIIa IgG synthesis by peripheral blood B cells from patients in vitro, 17,18 with the spleen as the primary site for the autoreactive B cells to receive such help in vivo.…”

Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4 and CX3CR1

“…CD4 ϩ T-helper cells from ITP patients have been shown to secrete interleukin 2 (IL-2) upon stimulation with autologous platelets. 5,6 Clonal expansion of CD4 ϩ T-helper cells has also been reported, 7 and it has been shown that T cells from ITP patients can proliferate in vitro by GPIIb/IIIa stimulation. 8,9 We have previously demonstrated that platelets in ITP can be destroyed directly by CD8 ϩ T cell-mediated cytotoxicity, 10 and that activation-induced cell death (AICD) of T cells is impaired.…”

Preferential splenic CD8+ T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia

“…The autoantibodies have undergone a class switch and somatic mutations, which requires B-and T-cell cooperation. 3 T lymphocytes in ITP patients display specific features, with a cytokine pattern skewed toward a Th1 profile, [4][5][6] an oligoclonal T-cell receptor (TCR) restriction, 5,7 and an engagement into antiapoptotic pathways.…”