Effects of hTNF alpha expression in T cells on haematopoiesis in transgenic mice

A transgenic line of mice carrying one copy of the hTNF alpha gene under th e control of its own promoter and the CD2 locus control region has been ana lysed for the effects of TNF alpha on haematopoiesis. A low level constitut ive expression of hTNF alpha in lymphoid tissue was observed. Human TNF alp ha binds to and activates the murine p55 receptor, but not the p75 receptor . This implies that the observed effects of hTNF alpha in mice were mediate d only through the p55 receptor. Various lymphoid tissues were depleted of lymphocytes, especially thymus, s pleen and peripheral blood. Effects on thymus development were detected alr eady 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 lym phocytes. At 16 wk the mice had developed anaemia, whereas platelets, neutr ophils and monocytes had increased. The fall in lymphocytes was due to lowe red levels of T cells as well as B cells. The cause of the shortened lifesp an of the transgenic mice was probably not the haematological effects of hT NF alpha directly. Absence of trophic factors supplied by the normal T cell population remains possible.