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Circulating CALLA-positive lymphocytes exhibit circadian rhythms in man
Abstract:
Common acute lymphoblastic leukemia antigen (CALLA) is a polypeptide with a molecular weight of 100,000 daltons (P100). It has been mainly found on the membrane of leukemic lymphoblasts, but not on that of normal circulating lymphocytes. Circadian rhythmicity in circulating CALLA-positive (CALLA+) lymphocytes was investigated in five healthy male subjects. Blood was sampled every 4 h for 24 h in each subject. Seven times series were obtained (three for the same subject). Leukocyte and differential counts were determined, and mononucular cells (greater than 95% lymphocytes) were isolated in Ficoll-Paque gradient. CALLA+ cells were characterized with both J5 and VILA1 monoclonal antibodies. Other T- and B-cell subpopulations were also determined in the same samples. Up to 1160 +/- 498 (mean +/- 1 S.E.M) J5-labelled CALLA+ lymphocytes per mm3 were found in peripheral blood at night. At this time, circulating VILA1-labelled CALLA+ lymphocytes also reached their peak although with a much lower number (66 +/- 14 cells/mm3). A circadian rhythm (with a period identical to 24h) was statistically validated with several methods for the number of J5-labelled cells, that of VILA1-labelled cells and the J5: VILA1 ratio. The count of J5-labelled CALLA+ cells was correlated with that of total lymphocytes, total T (OKT3+) and inducer T (OKT4+) cells (p less than 0.01), but neither with suppressor/cytotoxic cells (OKT8+) nor with B cells (SIg+, B1+, B2+, or HLA-Dr+). No correlation was found between any of these lymphocyte subpopulation and the count of VILA1-labelled CALLA+ cells. Such results further support the hypothesis that VILA1 and J5 monoclonal antibodies do not bind to the same epitope of the CALLA molecule. The large nocturnal increase in circulating J5-labelled CALLA+ lymphocytes may be accounted for by a release of immature presumably T lymphocytes in the peripheral blood.