SUMMARYZAP-70 de®ciency is a rare primary immunode®ciency characterized by the absence of peripheral CD8+ T cells and defects in T-cell receptor (TCR) signalling. T cells in ZAP-70-de®cient patients are assumed to have no helper functions for B-cell immunoglobulin synthesis, whereas the patients rarely have antigen-speci®c antibodies. We experienced a ZAP-70-de®cient patient, who had immunoglobulin E (IgE) antibodies speci®c to food allergens, and we investigated the mechanisms of switching to IgE in the patient. Peripheral blood mononuclear cells from the patient did not proliferate upon stimulation with the antigens but produced distinct levels of interleukin-4 (IL-4). Cell sorting analysis indicated that the cells that produced IL-4 in response to the antigens were enriched in CD4 + T cells. Puri®ed CD4 + T cells from the patient produced IL-4 and expressed CD40L upon stimulation with anti-CD3. Moreover, CD4+ T cells pretreated with anti-CD3 induced mature e transcript on naive B cells. Since the results indicated that there remained suf®cient T-cell receptor (TCR)-signalling in the patient's T cells to exert antigen-speci®c IgE switching on B cells, we next investigated the expression of the ZAP-70-homologous kinase Syk. Syk was present in high levels in patient's CD4 + T cells and was tyrosine-phosphorylated after TCR stimulation. Inhibition of Syk by piceatannol resulted in decreased production of IL-4 and expression of CD40L on patient's CD4 + T cells. Moreover, Syk was expressed on all human T-cell leukaemia virus (HTLV-1)-transformed T-cell lines derived from peripheral blood of the patient, whereas it was low or undetectable in control lines. It was therefore concluded that speci®c IgE responses in the patient were most likely to be mediated by Syk-dependent TCR-signalling.

SUMMARYThe aetiology of IgA nephropathy (IgAN) is closely related with abnormality of mucosal immunity. We investigated the roles of gd T cells in the regulation of IgA production by B cells in IgAN patients. The proportion of gd T cells in peripheral blood mononuclear cells (PBMNC) was higher in IgAN patients than in the controls and was found to be correlated with the proportion of surface IgA-positive (sIgA1) B cells, which are precursors of IgA-secreting plasma cells. After in vitro PWM stimulation, sIgA expression on B cells and IgA production were significantly enhanced in PBMNC obtained from IgAN patients, whereas the enhancements were abolished by removal of gd T cells from the PBMNC. Purified gd T cells from IgAN patients induced surface IgA expression on naõ Ève sIgD1 B cells more effectively than did ab T cells. Moreover, stimulated gd T cells from IgAN patients produced a larger amount of TGF-b 1, which is one of the main cytokines that induces IgA class switching on B cells, as compared with ab T cells and control gd T cells. The expanded gd T cells from IgAN patients exclusively expressed Vg9, and the nucleotide sequences of junctional regions of Vg9 showed very limited TCR diversities. It was therefore concluded that gd T cells, which are expanded in response to specific antigens, enhance IgA class switching on B cells in IgAN patients.

A 9-month-old boy presented with chronic arteritis of the aorta and its major branches. The clinical manifestations at onset of his illness were compatible with those of Kawasaki syndrome. However, the febrile period lasted for 2 months despite various immunosuppressive therapies, and the levels of C-reactive protein remain high 18 months after onset. Elevated circulating immune complexes, decreased serum complement levels, hypergammaglobulinaemia and monoclonal gammopathy were observed. Active HHV-6 infection was shown by increased serum levels of antihuman herpesvirus-6 (HHV-6) IgG and IgM antibodies, and positive HHV-6 DNA in sera, peripheral blood mononuclear cells (PBMNC) and lymph nodes. HHV-6 was actively replicating in PBMNC and lymph nodes, as shown by the detection of transcripts for the virus structural antigen. These results suggest that large vessel arteritis can be associated with HHV-6 infection.

SUMMARYRecent studies have suggested that a high percentage of Epstein-Barr virus (EBV)-infected lymphocytes in peripheral blood of patients with chronic, active EBV infection (CAEBV) is of T cell origin. Although T cells are expanded oligoclonally in CAEBV, it is not clear whether the restricted diversity of T cells arise from immune reaction against EBV-related antigens or from proliferation of EBVinfected cells. We experienced a patient with CAEBV who had biclonal expansion of peripheral blood T cells. We identified clonotypes of these two T cell clones in detail and purified the T cell clones. EBV infected mainly the two T cell clones, whereas the viral loads in peripheral blood cells other than these T cell clones were low or undetectable. The EBV strains infecting the two T cells clones were indistinguishable from each other by a series of genotype analyses of the virus. These results suggest that the two T cell clones infected with the same monoclonal EBV proliferated in peripheral blood of the patient.

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