Th2 suppressor cells are more susceptible to sphingosine than Th1 cells in murine contact photosensitivity

Murine contact photosensitivity (CPS) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) is a cutaneous delayed-type hypersensitivity reaction in which both positive and negative regulatory pathways exist, The latter pathway is mediated by antigen-specific, CD4+ suppressor T cells (CPS-Ts) that are Th2 cells. We examined the effects of sphingosine and synthetic cell-permeable analogs of ceramide on the cellular kinetics of CPS-Ts and immune lymph node cells from TCSA-photosensitized mice (CPS-LNC), along with other murine T-cell populations. The addition of sphingosine at 10 or 3 mu M to in vitro cultures suppressed DNA synthesis of CPS-Ts and Th2 clones, including D10 cells and 24-2 cells, but not: that of CPS-LNC or Th1 clones, including 23-1-8 and 28-4 cells. This suggested that sphingosine exerts its inhibitory effects preferentially on the proliferation of Th2 cells, Although suppressing DNA synthesis, sphingosine augmented the production and mRNA expression of interleukin-4 (IL-4) and enhanced the expression of the IL-4 receptor in CPS-Ts, In addition, the ability of sphingosine to induce signal transduction of CPS-Ts was confirmed by elevation of the intracellular free Ca++ concentration. Because CPS-Ts exposed to sphingosine exhibited a lower G(2)M/G(1) ratio than control, these seemingly ambivalent phenomena may be caused by retardation of the G(1) to S phase progression, a cell-cycle dysregulation known to augment cytokine production, In contrast to sphingosine, cell-permeable ceramide did not affect the proliferation of these cells when stimulated with mitogen/antigen and did not augment IL-4 production by CPS-Ts. Our study suggests that sphingosine modifies the Th1/Th2 balance by preferentially affecting the cellular kinetics of Th2.