Cytotoxic lymphocytes 356 Subject

The stress-associated shift in Thl/Th2 cytokines observed in human subjects has also been demonstrated in restraint-stressed mice. Associated with the shift towards a Th2 response are a significant decrease in NK cell activity, decreased IFN-y production by Con A-stimulated splenocytes, and a concomitant increase in serum corticosterone levels after 24 hours of restraint.30 These observations are consistent with studies on the effects of restraint stress and the immune response to viral infection. Restraint-stressed mice exhibited a decline in NK cell activity and a decrease in the generation of virus-specific cytotoxic T lymphocytes to HSV-l after primary infection, which resulted in an increase in the replication of the virus at the site of infection.3132... 

Interestingly, when the synthetically-derived allocolchicinoids ( )-19 and ( )-20 were subjected to the relevant binding assay they did not show inhibitory effects on tubulin polymerisation. Furthermore, they were not cytotoxic to L1210 (murine lymphocytic leukaemia) cells [34],... 

Evidence that purine metabolism is important in the immune response has been obtained from the observation that markedly reduced or absent adenosine deaminase (ADA) activity in man has been casually associated with an autosomal recessive form of severe combined immunodeficiency disease (3). Recently, ADA levels in lymphocytes from patients with untreated chronic lymphatic leukemia have been found to be consistently lower than in lymphocytes from normal subjects (4). Children with ADA deficiency and immunodeficiency have been shown to have increased levels in plasma, urine, lymphocytes and erythrocytes of adenosine, adenine, deoxy-adenosine, adenine nucleotides, and deoxyadenine (5, 6). Although the exact biochemical mechanism(s) is unknown, elevated levels of adenosine, and/or deoxyadenosine and their metabolites are thought to be selective inhibitors of both differentiation and effector function of lymphocytes (7, 8). Adenosine was known to inhibit the PHA-induced blastogenesis of human peripheral blood lymphocytes (9) even before the discovery of the first ADA-deficient child. In addition, elevated levels of cyclic AMP (cAMP) were known to be inhibitory for lymphocyte-mediated cytotoxicity (7). Since... 

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