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The in vivo antibody response to the primary T-cell dependent antigen Helix pomatia Haemocyanin (HPH) was studied, in order to detect the possible presence of a humoral immune deficiency in ageing. The IgG subclass distribution of the specific antibodies was also determined. In order to define a dose of HPH which could be used to discriminate between the responsiveness of healthy and immunocompromised individuals, we first established a dose-response curve for this antigen in 60 healthy young volunteers. Their responses were compared with the responses of a group of patients suffering from end stage renal failure. The patients who were treated with haemodialysis showed a significantly lower IgM, IgG and IgA anti-HPH antibody response after immunisation with a dose of 30 micrograms HPH, which could be restored by increasing the antigen dose. Patients treated with continuous ambulant peritoneal dialysis and a group of elderly persons, selected according to the Senieur protocol, showed no impairment of antibody formation after immunisation with 30 micrograms HPH, but in the non-Senieur elderly the anti-HPH antibody response was significantly lower. Furthermore, Senieur and non-Senieur elderly persons showed a diminished IgG2 anti-HPH antibody formation, whereas in the elderly non-Senieur individuals and in the patients with renal insufficiency, IgG1 and IgG3 anti-HPH antibodies were also diminished. This study clearly shows that the so-called age-associated immune deficiency can be the result of disease and is not necessarily due to the ageing process itself.

The antigen-specific antibody secretion in vitro after immunisation with the primary T-cell dependent antigen Helix pomatia Haemocyanin (HPH) was investigated in both young and elderly individuals, who all met the health admission criteria for immunogerontological studies as detailed in the SENIEUR protocol. In addition, elderly non-Senieur persons were incorporated in this study. Young and elderly Senieur volunteers were fully comparable in terms of the occurrence of anti-HPH antibody secreting cells after in vitro simulation of peripheral blood mononuclear cells with variable doses of the antigen. In contrast, the non-Senieur elderly showed a lower number of anti-HPH antibody secreting cells in vitro. PHA-conditioned medium did enhance this in vitro response, whereas the addition of IL-2 remained ineffective. The PHA-induced T-cell proliferation was found to be somewhat impaired in elderly Senieur individuals and significantly lower in elderly non-Senieur individuals compared to young healthy persons. Using an immunofluorescence double staining technique after BrdU incorporation, the phenotype of the proliferating cells was determined. Again the total number of proliferating cells was impaired in the non-Senieur elderly. No changes in the relative contribution of CD4+ or CD8+ cells to the number of proliferating cells were found in the different age groups. On the other hand, a significantly lower number of proliferating cells with IL-2 receptor expression were detected in the non-Senieur individuals, which could account for the lack of response to IL-2 in this group. Our study clearly shows that so-called age-associated immune deficiency can be the result of disease and not necessarily of the ageing process itself.

Serum levels of IgM and IgA classes and of IgG subclasses were determined and related to the presence of homogeneous immunoglobulin components (H-Ig) in volunteers equally distributed in age groups from 25 to 98 years, who all met the Senieur admission criteria for immunogerontological studies. In addition, sera of non-Senieur volunteers aged 75 years and older were included. Furthermore, the amount of IgD was determined in sera of Senieur individuals equally distributed in age groups from 15 to 98 years. In the Senieur persons, the contribution of the IgG subclasses and the IgM and IgA classes to the pool of serum immunoglobulins remained relatively unchanged during the course of ageing. In comparison with Senieur individuals aged 25-34 years, a slight increase in IgM and IgA levels was observed from the age 35 to 44 onwards and in IgG1 from the age 55 to 64 onwards. The variability of the immunoglobulin concentrations increased during ageing. The most prominent observation was the continuous decline of serum IgD starting in young adults. The non-Senieur persons differed from their Senieur age-matched counterparts mainly by the elevated IgG2 and IgA levels. During the course of ageing, H-Ig mainly of low concentration were detected at an increasing frequency in the Senieur persons and even more frequently in the elderly non-Senieur volunteers. Although in some individuals the elevation of immunoglobulin levels correlated with the appearance of H-Ig within the corresponding isotype, this relationship was not conclusive for all sera investigated. These results suggest that the rise of serum levels of individual immunoglobulin isotypes associated with ageing is usually the consequence of a polyclonal B cell activation. The occurrence of H-Ig and the decline of serum IgD in aged Senieur persons indicate that these are, at least partly, true phenomena of ageing and not always the consequence of disease.