Effects of hTNFα expression in T cells on haematopoiesis in transgenic mice

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Abstract
A transgenic line of mice carrying one copy of the hTNFalpha gene under the control of its own promoter and the CD2 locus control region has been analysed for the effects of TNFalpha on haematopoiesis. A low level constitutive expression of hTNFalpha in lymphoid tissue was observed. Human TNFalpha binds to and activates the murine p55 receptor, but not the p75 receptor. This implies that the observed effects of hTNFalpha in mice were mediated only through the p55 receptor. Various lymphoid tissues were depleted of lymphocytes, especially thymus, spleen and peripheral blood. Effects on thymus development were detected already at 3 wk of age, more general effects on haematopoiesis were evident by 5 wk: a drop in total blood leukocytes, mainly due to a 67% decline in lymphocytes. At 16 wk the mice had developed anaemia, whereas platelets, neutrophils and monocytes had increased. The fall in lymphocytes was due to lowered levels of T cells as well as B cells. The cause of the shortened lifespan of the transgenic mice was probably not the haematological effects of hTNFalpha directly. Absence of trophic factors supplied by the normal T cell population remains possible.

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