GANGLIOSIDES - DIFFERENTIATION MARKERS FOR MURINE-T HELPER LYMPHOCYTE SUBPOPULATIONS TH1 AND TH2

On the basis of the pattern of lymphokines they secrete, murine T helper clones can be divided into two subsets, T(H)1 and T(H)2. This concept of two different T helper effector cells helps to explain the diversity of immune reactions occurring in different parts of the body. The in vivo localization of T helper subtypes is of great interest, but up to now no biochemical or surface markers were available to distinguish between them. We analyzed the glycolipids from altogether 12 murine T(H)1 and T(H)2 cell lines or clones. A comparison of the gangliosides by thin-layer chromatography showed differences between the T(H)1 and T(H)2 cells. Binding studies with specific antibodies to asialo backbone structures after degradation by neuraminidases showed that the main gangliosides from these lymphocytes shared a common GgOse4 backbone and thus differed only in their degree or position of sialylation. Two disialogangliosides appeared to be characteristic. They were isolated from the D10.G4.1 T(H)2 cell clone and identified by fast atom bombardment mass spectrometry as IVNeuAc,IINeuAc-GgOse4Cer (G(D1a)) and IVNeuAc,IIINeuAc-GgOse4Cer (G(D1a)), respectively. G(D1a) was characteristically only detected in T(H)2 cells, whereas G(D1alpha) was preferably, but not exclusively, expressed by T(H)1 lymphocytes. Although G(D1a) was also found in the lung, heart, kidney, and spleen, its expression within the murine immune cells under investigation was unique to T(H)2 lymphocytes. Scarcely any G(D1a) was found in thymocytes, B cells, or CD8 positive (cytolytic) T cells, but significant expression was seen in CD4 positive (helper) T cells which include the T(H)2 subpopulation. According to these data, G(D1a) can be considered as a useful marker for the T(H)2 helper subtype in the mouse.