Gamma interferon and interleukin 2, but not interleukin 4, are detectable in gamma/delta T-cell cultures after activation with bacteria.

Mycobacterium tuberculosis- or group A streptococcus-activated gamma/delta T cells from normal healthy individuals were negatively sorted and restimulated in vitro from 48 h. Significant amounts of gamma interferon were detected after restimulation with M. tuberculosis, group A streptococci, or Listeria monocytogenes. In contrast, interleukin 4 was undetectable in the culture supernatants. Our findings provide indirect evidence for the involvement of gamma/delta T cells in immunity against tubercle bacilli and probably other bacteria.

Acanthocheilonema viteae (Dipetalonema viteae) in mice: differences in the relative binding of microfilarial surface-specific antibody may explain the contrasting response phenotypes of BALB/c and C57BL/10.

Experiments were carried out to obtain additional data concerning the role of IgM antibodies, specific for the cuticular surface of the microfilariae (mf) of A. viteae, in clearing microfilaraemia from high- and low-responder mice infected by transplanted adult worms. Although BALB/c mice, which sustain a chronic microfilaraemia, produced IgM mf surface-specific antibodies, the binding to target mf was weak when compared to that of antibodies from the serum of the resistant C57BL/10 mice. Furthermore, antibodies from BALB/c mice were not as efficient as those from C57BL/10 mice in promoting the adherence of immune or control leukocytes to mf in vitro. Evidence is provided to show that mf shed surface bound antibody. Although the results do not establish conclusively the mechanism underlying the contrasting response phenotypes of C57BL/10 and BALB/c mice, they provide support for the involvement of antibody in controlling microfilaraemia and suggest that quantitative and qualitative differences in the amount and affinity of IgM antibody specific for the mf surface, together with the natural tendency of the mf to shed surface bound antibody at 37 degrees C, may combine to allow the former strain to clear microfilaraemia efficiently whilst the latter sustains a chronic infection.

Target cell lysis and IL-2 secretion by gamma/delta T lymphocytes after activation with bacteria.

Peripheral blood T lymphocytes from healthy donors were stimulated with Mycobacterium tuberculosis in vitro and afterward analyzed phenotypically. Marked expansion of the gamma/delta T cell population (3- to 21-fold) was observed in 15/21 donors 7 to 10 days after stimulation. In addition to M. tuberculosis, Mycobacterium leprae (six of eight) as well as the gram-positive bacteria, Staphylococcus aureus (two of six), group A streptococci (seven of nine), and Listeria monocytogenes (four of eight) augmented gamma/delta TCR expression in peripheral blood T cells of many donors. gamma/delta T lymphocytes expressed IL-2R and secreted IL-2 upon restimulation with M. tuberculosis. Stimulation with M. tuberculosis evoked specific cytolytic activities in gamma/delta T lymphocytes because: gamma/delta T cells lysed M. tuberculosis pulsed but not unpulsed targets; high concentrations of TCR delta 1 mAb facilitated killing of unpulsed target cells; and low doses of anti-TCR delta 1 mAb blocked killing of pulsed targets. Furthermore, gamma/delta T cells from four donors, after activation with M. tuberculosis or with group A streptococci, respectively, only lysed targets pulsed with the homologous agents, whereas in other donors some cross-reactivity was observed. We conclude that, upon contact with mycobacteria and perhaps other microorganisms, gamma/delta T cells are activated which contribute to immunity against infection via IL-2 secretion and specific target cell lysis.

Immunity to mycobacteria: possible role of alpha/beta and gamma/delta T lymphocytes.

Immunity to pathogenic mycobacteria is mediated by T lymphocytes. The possible contribution of CD4 alpha/beta T cells, CD8 alpha/beta T cells and gamma/delta T cells as well as the possible role of interleukin-mediated macrophage activation and target cell lysis through direct cell contact is discussed. Furthermore, attempts to define mycobacterial antigens for T lymphocytes with particular emphasis on heat shock proteins are described. The data currently available suggest complex interactions between different T-cell types in immunity to mycobacteria.

A histocytochemical study of the macrophages present in tissue responses to adult Onchocerca volvulus.

Immunocytochemical and histochemical properties of macrophages present in the subcutaneous chronic inflammatory responses surrounding adult Onchocerca volvulus (nodules) in human tissues were examined. Macrophages with strong non-specific esterase (NSE) and acid phosphatase (AcPase) activities but weak adenosine triphosphatase (ATPase) activity and HLA-DR expression (NSE+++, AcPase+++, ATPase-/+, HLA-DR-/+) were present in the centre of nodules. Many of the cells adhering to the surface of worms were NSE+++, AcPase+++, ATPase-, HLA-DR+++. The inner zone of the fibrous capsule of nodules contained macrophages with the profile NSE+++, AcPase-, ATPase-/+, HLA-DR-/+. A fourth type, NSE+++, AcPase-/+, ATPase-/+, HLA-DR+++, was located in the outer zone of the capsule, frequently within perivascular accumulations of macrophages, lymphocytes and plasma cells. Active fibroblasts were identified at the inner edge of the fibrous capsule by alkaline phosphatase staining. A feature of all nodules examined was the presence of lipid-filled macrophages, demonstrated by Oil Red O stain; these cells were usually situated in zones adjacent to the centre of nodules, and were of the NSE++, AcPase++, ATPase-/+, HLA-DR-/+ type. Lipid accumulation was not found to be related to the clinical status of the patients studied. The origin and functional significance of this lipid is unknown.

Mononuclear and multinuclear macrophages in filarial infections.

Filarial infections commonly involve chronic tissue responses to these complex and resiliant organisms. These responses, which occur with a number of the parasitic stages of filariae, involve macrophages, and these cells appear to be important in immunologically induced destruction and removal of these important parasites of man and animals. Details of their presence and experimental induction as well as their distinction into a number of morphological types, including multinuclear (giant cell) forms, is described in this communication. The ability of these various forms to function in phagocytic and immunologically mediated adherence assays is also described.

A comparison of the antibody responses of badgers (Meles meles) and rabbits (Oryctolagus cuniculus) to some common antigens.

The primary and secondary antibody responses of rabbits and badgers were compared after intravenous inoculation of inactivated influenza A virus, sheep erythrocytes (SRBCs), bovine serum albumin (BSA) or bacteriophage psi X174. BSA was also given as a primary injection by the intramuscular route in solution or in Freund's incomplete or complete adjuvant, followed by an intravenous secondary inoculation without adjuvant. Antibody responses were monitored by: haemagglutination inhibition and neutralization tests for influenza virus; direct and antiglobulin haemagglutination tests for SRBCs; indirect haemagglutination test and the Farr method for antigen-binding capacity (ABC) for BSA; neutralization of psi X174. Rabbits gave good responses to all antigens, but the response of badgers was generally poor. After intravenous administration, badgers gave a good response only to psi X174, but even then they produced less antibody than rabbits receiving 100 times less antigen; the immune elimination of phage was more rapid and antibody appeared about 48 h earlier in rabbits than in badgers. Intramuscular administration of BSA and the use of adjuvants improved the badgers' response, with greatest improvement in ABC. These results indicate that badgers display relatively poor immune responses to a variety of antigens.