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 microM 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 Thl 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 G2M/G1 ratio than control, these seemingly ambivalent phenomena may be caused by retardation of the G1 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.
Tokura
Y
Y
Department of Dermatology, Hamamatsu University School of Medicine, Japan.
Wakita
H
H
Yagi
H
H
Nishimura
K
K
Furukawa
F
F
Takigawa
M
M
D000485:Allergens / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002518:Ceramides / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D016193:G1 Phase; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D010787:Photosensitivity Disorders / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D018123:Receptors, Interleukin / Q000378:metabolism; D019948:Receptors, Interleukin-4; D016196:S Phase; D012458:Salicylanilides / Q000276:immunology; D013110:Sphingosine / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000187:drug effects* / Q000473:pathology
D000485:Allergens; D015703:Antigens, CD; D002518:Ceramides; D016207:Cytokines; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D012458:Salicylanilides; C003390:3,3',4',5-tetrachlorosalicylanilide; D013110:Sphingosine; D002118:Calcium