Selective expansion of human γΔ T cells by monocytes infected with live Mycobacterium tuberculosis

Abstract

Gamma delta (γδ) T cell receptor (TCR) expressing T cells comprise 3% of human peripheral blood lymphocytes, yet their role in the immune response remains largely unknown. There is evidence both in humans and in animal models that these cells participate in the immune response to mycobacterial antigens. In mice, exposure to mycobacterial antigens leads to the expansion of γδ T cells in draining lymph nodes and lungs. In humans, γδ T cell lines with reactivity to mycobacterial antigens have been derived from synovial fluid of a rheumatoid arthritis patient, skin lesions of leprosy patients, and peripheral blood of a healthy tuberculin reactor. Very little is known, however, about the factors which induce human γδ T cells to expand. In studies comparing the human T cell response to live and heat-killed Myobacterium tuberculosis (MT), we have found that monocytes infected with live MT are very effective inducers of human γδ T cell expansion. After 7 d of exposure to live MT, γδ T cells were greatly increased in all healthy tuberculin reactors (PPD+) tested and frequently were the predominant T cell population. In contrast, heat-killed MT or purified protein products of MT induced a CD4+, αβTCR+ T cell response with very little increase in γδ T cells. Furthermore, a similar selective induction of γδ T cells was observed when monocytes infected with live Salmonella were used to stimulate T cells. Heat-killed Salmonella, like heat-killed MT, induced a predominantly CD4+ αβTCR+ T cell response. These findings suggest that human γδ T cells are a major reactive T cell population during the early stages of infection with living intracellular bacteria and are therefore likely to exert an important role in the initial interaction between host and parasite.