The proportion of circulatingγδT cells increases after the first week of onset of tularaemia and remains elevated for more than a year

Abstract

SUMMARYIn various human intracellular bacterial diseases, an increase of the proportion of circulating Vg9Vd 2 T cells has been observed. The prevalence of the finding among infected subjects and the time course of the elevation remain to be investigated. In the present study, comprising blood samples from a large number of cases of ulceroglandular tularaemia, the percentage of Vg9Vd 2 T cells within the first week of onset of disease (5´3^0´7% (mean^s.e.m.)) did not differ from that of control subjects (5´3^0´8%). Thereafter, percentages increased rapidly and within the interval of 8±40 days mean levels were . 20% (P , 0´001). Of 45 individuals sampled within 3 months of onset, 42 showed a percentage of Vg9Vd 2 T cells of . 10%. Significantly increased levels were still recorded at 18 months (13´8^2´4%; P , 0´05) but not at 24 months (10´2^2´1%; P . 0´10). Thus, a consistent increase of circulating Vg9Vd 2 T cells was demonstrated in tularaemia. The initial delay and the prolonged course of elevation may suggest a role in immunoregulation and/or immunological memory. Furthermore, the percentage of gd T cells expressing tumour necrosis factor-alpha in response to phorbol myristate acetate was decreased during the first week and up to 40 days after onset, possibly reflecting the modulation of an inflammatory response.

Transcriptional profiling of the peripheral blood response during tularemia

“…31 It appears as if they play a part in the early immune response to infection, perhaps by initially secreting high levels of cytokines such as IFN-g and TNF-a, and subsequently downmodulating this secretion. 32 Notable, RNA levels were much higher in the patient convalescent samples obtained 3 months after recovery than in the pooled control RNA sample. This agrees with the previous demonstration that markedly higher levels of Vg9Vd2 T cells persisted in peripheral blood at least 18 months after tularemia.…”

“…32 A prominent increase of circulating Vg9Vd2 T cells occurred between days 8 and 40 and the increase persisted up to 18 months after infection. Considering that these changes are so long-lasting, they may be one likely explanation for some of the transcriptional changes observed in the convalescent samples.…”

“…This agrees with the previous demonstration that markedly higher levels of Vg9Vd2 T cells persisted in peripheral blood at least 18 months after tularemia. 32 We performed Q-PCR analysis of cytokine gene expressions (Table 3). We found a significant change in mRNA levels for IFN-g, TNF-a, IL-1b and IL-15.…”

Leptospira interrogansActivation of Human Peripheral Blood Mononuclear Cells: Preferential Expansion of TCRγδ+ T Cells vs TCRαβ+ T Cells

“…Increased numbers of peripheral blood TCR␥␦ T cells have been documented in a number of different bacterial infections (25,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). Our results poise the important question of whether TCR␥␦ ϩ T cells are also elevated in the peripheral blood of leptospirosis patients.…”

“…Not surprisingly, we show that V␥9/V␦2 are expressed by all TCR␥␦ ϩ T cells expanded by Leptospira. Significant increases in the number of peripheral blood V␥9/V␦2 T cells have been documented in humans in many bacterial and parasitic diseases, such as tuberculosis and malaria (23,(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). In this study we show that patients with acute leptospirosis have increased numbers of peripheral blood TCR␥␦ ϩ T cells.…”