T4+ CELL NUMBERS ARE CORRELATED WITH PLASMA GLUTAMATE AND CYSTINE LEVELS - ASSOCIATION OF HYPERGLUTAMATAEMIA WITH IMMUNODEFICIENCY IN DISEASES WITH DIFFERENT ETIOLOGIES

Human immunodeficiency virus type 1 (HIV-1) seropositive individuals suffer from a depletion of T4+ T cells and have elevated plasma glutamate levels. Glutamate is also elevated in cancer patients, and several authors have shown that elevated extracellular glutamate levels inhibit competitively the membrane transport of cystine and cause a decrease of intracellular cystine. We, therefore, tested the hypothesis that high glutamate and/or low cystine levels may generally be associated with low lymphocyte reactivity or low T4+ counts. In three independent studies we tested (i) serum amino acid levels (AAL) versus T4+ counts in healthy individuals, (ii) plasma AAL versus lymphocyte responses in healthy individuals, and (iii) plasma AAL versus T4+ counts in HIV-1 seropositive individuals. When the individuals in each study were divided into four subgroups as defined by median glutamate and cystine levels, the results showed that persons with a combination of low glutamate and high cystine level (LGHC subgroups) had the highest mean T4+ count or highest lymphocyte reactivity. Moreover, the LGHC subgroup in a study of lung cancer patients had a much longer mean survival time than the other three subgroups. In HIV-1 infected patients, hyperglutamataemia is associated with hypocystinaemia and hypocysteinaemia. Azidodeoxythymidine (AZT) treated HIV patients had, on average, lower glutamate levels than patients without AZT. The data from patients and in vitro experiments together with the observation that T4+ cell counts and lymphocyte reactivity are inversely correlated with individual glutamate and positively correlated with cystine levels even in healthy individuals suggest strongly that hyperglutamataemia may be a causative factor and may act by inhibiting cystine transport.