Based on the combined expression of CD27 and CD28, a putative model of T cell differentiation has been previously proposed. We used CD27 and CD28 expression in order to comparatively study the size, cytokine production capacity and proliferative response of CD4+ T cell sub-populations from healthy young and elderly volunteers. Elderly persons had a lower percentage of CD27+CD28+ but a higher percentage of CD27-CD28+ and CD27-CD28-CD4+ T cells than the young persons. CD27-CD28-CD4+ T cells were present, although at relatively low numbers, in the vast majority of the healthy elderly donors but were only sporadically detected in young persons. Each CD4+ T cell sub-population exhibited a distinct phenotype and cytokine production profile, which were not affected by age. When purified CD27+CD28+ were stimulated by staphylococcal enterotoxin B, they proliferated to a greater extent than CD27-CD28+ and CD27-CD28-CD4+ T cells. However, we did not observe age-related differences in proliferative response of each sub-population. We concluded that although the size of the different sub-populations differed between the young and the old group, the functional characteristics of each sub-population were the same in both age groups. This suggests that on a per cell basis there is no functional impairment of CD4 memory T cells in elderly persons. Consequently, potential differences in the function of the total CD4+ T cell population are most likely due to different composition of repertoire.
Alley running has been successfully used as an operant to demonstrate both the positive and negative reinforcing effect of intravenously administered drugs of abuse in a bona fide operant conditioning paradigm, the Ettenberg runway, in which confounding drug effects on motor performance and drug accumulation are avoided. While Ettenberg and colleagues focus on the intravenous route of drug administration, we tested the practicability of the subcutaneous route of administration in this runway paradigm in Sprague Dawley rats, using morphine as the investigated drug of abuse. We also modified the Ettenberg runway, most notably in that either food (sweetened condensed milk), no food, morphine, or saline was presented outside the runway in a separate cage. This made shaping, i.e., the initial presentation of a food reinforcer within the runway, necessary to establish responding. The manipulations necessary to administer subcutaneous (sc) injections were well tolerated by over 90% of the tested rats (n = 93). However, sc injections increased runtimes to the experimenter cutoff of 60 s within 20 once-daily sessions. Because of strong experimenter effects, all morphine doses or saline had to be adminstered blind. Under these experimenter-blind conditions, 0.1 and 1 mg/kg subcutaneous morphine proved to be reinforcing in that these doses significantly slowed down the gradual increase in runtimes imposed upon by the sc injection procedure. Thus, morphine can be demonstrated to be a positive reinforcer in a modified Ettenberg runway even when given subcutaneously. This effect, however, is eventually overcome by the negative reinforcing effect of subjecting the animals to sc injection procedure.
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