SELECTIVE EXPANSION OF HUMAN GAMMA-DELTA T-CELLS BY MONOCYTES INFECTED WITH LIVE MYCOBACTERIUM-TUBERCULOSIS

Gamma delta (gamma-delta) 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 gamma-delta-T cells in draining lymph nodes and lungs. In humans, gamma-delta-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-gamma-delta-T cells to expand. In studies comparing the human T cell response to live and heat-killed Mycobacterium tuberculosis (MT), we have found that monocytes infected with live MT are very effective inducers of human-gamma-delta-T cells expansion. After 7 d of exposure to live MT, gamma-delta-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+, alpha-beta-TCR+ T cell response with very little increase in gamma-delta-T cells. Furthermore, a similar selective induction of gamma-delta-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+ alpha-beta-TCR+ T cell response. These findings suggest that human-gamma-delta-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.