Gamma delta T lymphocytes in human tuberculosis.

The manifestations of tuberculous infection reflect the immune response to infection. Most healthy tuberculin reactors develop protective immunity; tuberculous pleuritis reflects a resistant response manifest by mild disease, whereas advanced pulmonary and miliary tuberculosis reflect ineffective immunity. The role of gamma delta T cells was assessed in tuberculous infection by evaluating expansion of these cells from blood mononuclear cells after stimulation with Mycobacterium tuberculosis. After culture in vitro, the percentages of gamma delta+ cells were significantly greater in patients with protective and resistant immunity (tuberculin reactors, 25% +/- 4%; tuberculous pleuritis, 30% +/- 7%) than in those with ineffective immunity (advanced pulmonary tuberculosis, 9% +/- 3%; miliary tuberculosis, 2% +/- 1%). In leprosy, expansion of gamma delta+ cells was greater in immunologically resistant tuberculoid patients (32% +/- 4%) than in Mycobacterium leprae-unresponsive lepromatous patients (9% +/- 2%). M. tuberculosis-reactive gamma delta T cell lines produced interferon-gamma, granulocyte-macrophage colony-stimulating factor, interleukin-3, and tumor necrosis factor-alpha, cytokines that activate macrophages and may contribute to mycobacterial elimination. These findings suggest that gamma delta T cells contribute to immune resistance against M. tuberculosis.

Evidence for clonal selection of gamma/delta T cells in response to a human pathogen.

T cells bearing gamma/delta antigen receptors comprise a resident population of intraepithelial lymphocytes in organs such as skin, gut, and lungs, where they are strategically located to contribute to the initial defense against infection. An important unsolved question about antigen-driven gamma/delta T cell responses regards the breadth of their T cell receptor (TCR) repertoire, since many specific epithelial compartments in mice display limited diversity. We have examined the diversity of TCR delta gene expression among human gamma/delta T cells from skin lesions induced by intradermal challenge with Mycobacterium leprae. We show that the vast majority of gamma/delta cells from M. leprae lesions use either V delta 1-J delta 1 or V delta 2-J delta 1 gene rearrangements and, within a given region of the lesion, display limited junctional diversity. This contrasts markedly with the extensive diversity of gamma/delta T cells from peripheral blood of these same individuals, as well as skin from normal donors. These results indicate that the gamma/delta response to M. leprae involves the selection of a limited number of clones from among a diverse repertoire, probably in response to specific mycobacterial and/or host antigens.

Inhibition of the interaction of mycobacteria with Schwann cells by antimycobacterial antibodies.

The effect of antimycobacterial serum on the uptake of Mycobacterium w by 33B rat Schwannoma cell line and rat peritoneal macrophages was studied. Incubation of Mycobacterium w with antimycobacterial serum caused a marked inhibition of its uptake by 33B cells but did not diminish its uptake by macrophages. These results suggest that the mechanism of the interaction of mycobacteria with Schwann cells differs from that with macrophages.

Interleukin 1--a possible mediator of neural fibrosis in leprosy.

Neural fibrosis in leprosy, the disease caused by the obligate intracellular bacterium, Mycobacterium leprae, is closely related to the cell-mediated immune response to this microorganism. The fibrosis appears to be due to soluble mediators released by the immune effector cells. Interleukin 1, a macrophage product that stimulates fibroblast migration, proliferation and synthetic activity, possesses the requisite properties to qualify for such a mediator.