Accessory function and properties of monocytes from healthy elderly humans for T lymphocyte responses to mitogen and antigen.

The waning of cell-mediated immunity during aging has been attributed primarily to defects in T lymphocyte properties and functions. We assessed the potential contribution of accessory dysfunction of monocytes from the elderly on responses of T cells to phytohemagglutinin (PHA) and to tetanus toxoid after in vivo boosting. Accessory function of monocytes from the elderly subjects for T lymphocyte responses to tetanus toxoid was comparable to the young. Expression of the cytokines interleukin-1, interleukin-6 and tumor necrosis factor, the cell adhesion molecules ICAM-1 and LFA-3 and the class II major histocompatibility molecule HLA-DR by monocytes from the elderly and young subjects was similar. T lymphocytes from the elderly responded poorly to PHA. Monocytes from the elderly had a decreased accessory function for PHA-stimulated T cells from young, third donors. Thus, although many accessory properties of monocytes from the elderly are normal, the monocyte and T lymphocyte defects in the elderly for mitogen may represent interactive factors in cell-mediated immunity during aging.

Transient normalization of lymphocyte blastogenic and specific antibody responses following boosting of healthy elderly subjects with tetanus toxoid.

The diminished in vitro blastogenic response of lymphocytes from the elderly to mitogenic stimuli is cited as evidence of immunosenescence, but the response to specific microbial antigens has not been well characterized. We measured the response to tetanus toxoid before and after boosting in young and elderly subjects. Elderly subjects (age > or = 70) and young controls (age < 35) were subjected to clinical, laboratory, and nutritional evaluation to ensure a cohort of healthy subjects. Responses of lymphocytes from the elderly to the mitogens phytohemagglutinin and concanavalin A were markedly diminished compared to those from the young. For all subjects, the average in vitro blastogenic response to tetanus toxoid of lymphocytes from elderly subjects (n = 23) was significantly diminished compared to young controls (n = 23; 31,985 +/- 4502 vs 14,411 +/- 3714 cpm, p < .01). Following boosting with tetanus in those subjects in whom boosting with tetanus toxoid was indicated, blastogenesis was comparable between elderly (n = 17) and young subjects (n = 7; 38,078 +/- 11,451 vs 42,103 +/- 9247 cpm). The boosted response to tetanus apparently was not sustained, since in the subset of subjects with a history of tetanus immunization in the past 10 years, the response of the elderly was much less than that of the young. Thus, a cohort of healthy elderly with diminished blastogenic responses to mitogens was capable of at least a transiently normal response to tetanus post boosting.

Role of the mononuclear phagocyte as an antigen-presenting cell for human gamma delta T cells activated by live Mycobacterium tuberculosis.

gamma delta T cells, both human and murine, have been found to be highly responsive to mycobacterial antigens. However, the role and function of gamma delta T cells in the immune response to Mycobacterium tuberculosis remain largely unknown. In earlier studies, we demonstrated that monocytes infected with live M. tuberculosis were particularly effective inducers of human peripheral blood gamma delta T cells. The present studies were performed to further characterize the interaction between human mononuclear phagocytes, gamma delta T cells, and live M. tuberculosis, in comparison with CD4+ T cells. First, we found that resting gamma delta T cells expanded in vitro by live M. tuberculosis were specific for M. tuberculosis, and that heat killing and washing the mycobacteria removed the antigen(s) for gamma delta T cells. In contrast, the heat-killed mycobacteria retained significant antigenicity for CD4+ T cells. Second, live M. tuberculosis-expanded gamma delta T cells from healthy tuberculin-positive donors did not respond significantly to the antigens in M. tuberculosis culture filtrate, including the 65- and 71-kDa mycobacterial heat shock proteins. Third, the activation of gamma delta T cells by live mycobacteria was dependent on antigen-presenting cells, and mononuclear phagocytes were found to be very efficient antigen-presenting cells both for resting peripheral blood gamma delta T cells and for activated expanded gamma delta T cells. The mononuclear phagocyte carried the necessary costimulatory factors necessary for gamma delta T-cell proliferation. Fourth, the antigen repertoire and HLA requirements for CD4+ memory T cells and those for gamma delta T cells appear to be quite distinct from each other. CD4+ T cells recognized both soluble protein antigens and whole organisms in a class II major histocompatibility complex-restricted manner, whereas gamma delta T cells appeared to recognize only constituents associated with the whole organism and were not restricted by class I or class II major histocompatibility complex molecules. Finally, the assay system described to expand and purify responding CD4+ and gamma delta T cells after stimulation with live M. tuberculosis represented a simple approach to the direct comparison of these two T-cell populations in the interaction with mononuclear phagocytes infected with M. tuberculosis. Such studies provide insight not only into the relative roles of human CD4+ and gamma delta T cells in the human immune response to intracellular bacterial pathogens such as M. tuberculosis but also into the basic biologic role of human gamma delta T cells in antimicrobial immunity.