Vγ9Vδ2 T Cells in Human Legionellosis

Abstract

ABSTRACT In humans, expansion of circulating Vγ9Vδ2 T cells seems to be a pathophysiological denominator shared by protozoan and intracellular bacterial diseases. The assumption was tested here on legionellosis, a condition conforming to the category but not yet described with respect to γδ T cells. Levels of Vγ9Vδ2 T cells in peripheral blood were measured at various intervals in 14 subjects undergoing a Pontiac fever-like disease, shown by serological investigation to be caused by Legionella micdadei . In samples obtained 4 to 6 days after the onset of the disease, the mean percentage (± the standard deviation) of Vγ9Vδ2 + T cells among CD3 + cells was 1.0% ± 0.5%, compared to 5.0% ± 3.9% in healthy control subjects ( P < 0.001). Thereafter, a pronounced increase occurred and at 2 to 7 weeks after onset, mean peak levels were as high as ≈15%. During the next 6 months, values slowly declined, although without reaching the normal range. Percentages of γδ + T cells expressing tumor necrosis factor alpha or gamma interferon in response to phorbol myristate acetate were assayed in vitro. At 14 to 16 days after the onset of disease, the expression of both cytokines was increased ( P < 0.01), whereas at 5 to 7 weeks, the expression of tumor necrosis factor alpha was decreased ( P < 0.05), possibly reflecting modulation of an inflammatory response. In conclusion, Pontiac fever was found to be associated with a pronounced and long-lasting expansion of Vγ9Vδ2 T cells, implying that the subset may also be pathophysiologically important in a mild and transient form of intracellular bacterial diseases. Surprisingly, the expansion was preceded by a depletion of circulatory Vγ9Vδ2 T cells. Possibly, Vγ9Vδ2 T cells are initially recruited to a site of infection before they expand in response to antigen and occur in high numbers in blood.