Search

Convalescent sera obtained from patients who were recently recovered from an acute measles virus infection were tested for the presence of anti-HIV-1 antibodies by Western blot analysis. While 16% (17/104) of control sera displayed reactive bands to a variety of HIV proteins, 62% (45/73) of convalescent sera demonstrated immunoreactive bands corresponding to HIV-1 Pol and Gag, but not Env antigens. This cross-reactivity appears to be the result of an active measles infection. No HIV-1 immunoblot reactivity (0/10) was observed in sera obtained from young adults several weeks after a combined measles, mumps, and rubella (MMR) vaccination. Interestingly, examination of anti-HLA typing sera specific for either class I and class II molecules revealed that 46% (19/41) of these sera contained cross-reactive antibodies to HIV-1 proteins. Absorption of measles sera with mixed lymphocyte reaction (MLR)-activated lymphocytes and/or HIV-1 recombinant proteins significantly decreased or removed the presence of these HIV-1-immunoreactive antibodies. Together, these findings suggest that the immune response to a natural measles virus infection results in the production of antibodies to HIV-1 and possibly autoantigens.

Sorted OKT4+ cells treated with pokeweed mitogen (PWM) and subsequently X-irradiated were used as a source of helper T cells to examine human T and B cell function. PWM-induced immunoprotein synthesis by human peripheral blood lymphocytes was the model used to study the cellular interactions. PWM was shown to induce helper T cell function which caused non-PWM treated B cells to secrete immunoglobulin. PBL from certain individuals could not be induced by PWM to secrete Ig therefore allogeneic co-cultures of helper T cells and B cells were examined to define the defective cell population. Ig synthesis in allogeneic cultures of T and B cells was always greater than that observed in autologous cultures when cells from responders were assayed. However, when allogeneic cultures were initiated using B cells from a responder and PWM treated T cells from a non-responder and examined for Ig synthesis, the B cell responses were markedly lower than seen in the autologous responder cultures. In addition, PWM activated helper T cells from a responder induced a significantly higher Ig synthesis by B cells from a non-responder. These observations indicate that PBL from individuals who do not respond in a PWM driven Ig synthesis assay have relatively normal B cell function but are deficient in helper T cell function.

High affinity interleukin 2 receptors (HA-IL-2R) on mitogen- or antigen-stimulated T cells have been shown to efficiently bind interleukin 2 (IL-2) and to transduce the activation signal(s) that facilitate proliferation. This study was initiated to determine whether the impaired proliferative response of T cells from elderly individuals can be attributed to the defective expression of HA-IL-2R. While cells from both young and old individuals had statistically insignificant differences in the number of HA-IL-2R per membrane IL-2R-positive cell and these receptors displayed similar binding affinities with 125I-IL-2, there were consistently fewer cells and fewer cells expressing HA-IL-2R in the cell cultures from elderly individuals. The magnitude of the age-associated impairment in cell proliferation was decreased, but remained present, when Percoll fractionated lymphoblasts, as compared to peripheral blood lymphocytes (PBL), were cultured in the presence of exogenous interleukin 2 (IL-2). The results demonstrate that a significantly larger percentage of lymphocytes from elderly individuals do not respond to mitogenic stimulation and, probably due to stimulus stress, die in culture. As a consequence there are fewer functionally competent cells expressing the HA-IL-2R in cultures from elderly individuals, which in turn contributes to the age-related defect in the lymphocyte proliferative response.

Human peripheral blood T lymphocytes were treated with phorbol myristate acetate (PMA), an activator of protein kinase C (PKC) activity, and with the calcium ionophore A23187. The resulting accumulation of specific mRNA for interleukin 2 (IL-2) and interleukin 2 receptor (IL-2R), as well as IL-2 secretion and membrane IL-2R expression were examined. At low concentrations (0.1 microM), A23187 synergized maximally with PMA to induce proliferation, to increase IL-2R mRNA levels and the expression of membrane IL-2R, and to produce a low but sufficient accumulation of IL-2 mRNA and IL-2 secretion. A high concentration of A23187 (1.0 microM) did not show any synergism for the accumulation of IL-2R mRNA, membrane IL-2R expression and inhibited the proliferation of PMA co-stimulated T cells. It did, however, induce maximum accumulation of IL-2 mRNA and IL-2 secretion.

The effect of age on the proliferative response to 12-O-tetradecanoyl phorbol-13-acetate (TPA) was examined using peripheral blood lymphocytes from 185 adults. TPA-induced DNA synthesis measured by cellular 3H-thymidine incorporation was found, like the responses of cells activated by PHA and Con A, to markedly diminish with advancing age. The presence of indomethacin (1 microgram/ml) or Ro 20-5720 (10 micrograms/ml) in TPA activated cell cultures, unlike PHA stimulated cultures, did not result in augmentation of 3H-thymidine incorporation by cells from elderly individuals. These results demonstrate that prostaglandin synthesizing suppressor cells are not responsible for the age-related depression of cellular immune function observed in TPA activated cells and confirm the observation that decreased production and/or utilization of soluble mediators, such as IL-2, may account for the diminished mitogen responsiveness of lymphocytes from elderly individuals.

Current models of T cell activation implicate increases in intracellular free Ca2+ concentration and activation of the Ca2+ and phospholipid dependent enzyme protein kinase C (PKC) as important early events leading to interleukin 2 (IL-2) production, interleukin 2 receptor (IL-2R) expression, and subsequent cell proliferation. The present study examined the age-related defect in T cell proliferation to determine if signals that activate PKC and increase intracytosolic free Ca2+ concentration might be defective. Using phorbol myristate acetate (PMA), which directly activates PKC, and Ca2+ ionophore A23187, which increases intracellular cytoplasmic free Ca2+ concentration, the induction of IL-2 secretion, IL-2R expression and cell proliferation were studied. The results demonstrate that following stimulation with PMA and A23187, purified T cells from elderly subjects demonstrate low levels of IL-2 production, IL-2R expression and cell proliferation. Exogenous purified human IL-2 did not fully correct the low proliferative responses of T cells from old donors, however, did markedly boost the response. While it appears that the inability of T cells to express IL-2R and respond to IL-2, along with a lower endogenous IL-2 production are limiting factors in cell proliferation, the inability of PMA and A23187 to correct this defect suggests that the early phases of signal transduction per se are probably not a primary cause of the immunodeficiency seen in ageing.

The effect of age on the in vitro generation of immunoglobulin-secreting cells in pokeweed mitogen-stimulated cultures was examined using a staphylococcal protein A plaque assay. Although there was no statistically significant decrease with age in the numbers of plaque-forming cells, subjects whose cells failed to produce immunoglobulin were four times more common amongst individuals over 55 years of age. Simultaneously-measured T and B lymphocyte numbers. 3H-thymidine incorporation by mitogen-stimulated cultures, and serum immunoglobulins were comparable in both the young and the aged.