Persistent T lymphocyte rhythms despite suppressed circadian clock outputs in rats

Abstract

Circadian rhythms in circulating leukocyte and lymphocyte counts persisted with halved amplitudes in constant light (LL) of 300 lx intensity for 8 wk, whereas circadian rhythms in body temperature, locomotor activity, and plasma catecholamines were completely suppressed. Subsequent exposure to constant darkness (DD) normalized all circadian rhythms within 2 wk. Rhythms in circulating T lymphocyte subsets were studied in LL or DD using double labeling with monoclonal antibodies and flow cytometry. Circadian rhythms were suppressed for leukocytes and lymphocytes but were maintained for both T helper cells (Th) and T cytotoxic cells (Ts) lymphocytes after 11 wk in LL. A group 24-h rhythm was only validated for total lymphocytes after 16 wk in LL. However, individual total, Th, and Ts lymphocytes maintained their usual respective phase relationships in each rat. The alteration of immune cell circulatory rhythms likely stemmed from a progressive loss of circadian synchronization among rats kept in LL. Conversely, after 11 or 16 wk in DD, leukocytes and lymphocyte subsets circadian rhythms were maintained. Thus catecholamines do not drive circulatory T cell rhythms. The loss of coupling between T lymphocyte rhythms and three major outputs of the circadian system further supports the hypothesis of an independent immunologic oscillator.