DONALD METCALF 



faster than irradiated control mice. Cell-free thymus extracts, when injected 

 into irradiated mice, produce similar effects. Lymph-node grafts or injec- 

 tions of lymph-node extracts do not alter the acute lymphopenic phase 

 following irradiation. Thymectomy increases the degree and the duration 

 of post-irradiation lymphopenia. 



These findings suggest that with this dosage of whole-body irradiation, 



60 



ST ^0 



20 



75 -c 



■o >, 



^ - -20 



•J a;-^o 



i_ x: 



o! c-eo 



0) 

 Q. 



Acute 

 phase 



Baseline level unirradiated 



mice 



Chronic phase 



01 23456789 10 

 Months after whole -body irradiation 



Figure 1. Biphasic response in peripheral lymphocyte 

 levels in the mouse following whole-body irradiation 



part at least of the observed lymphopenia is due to depression of some non- 

 cellular factor pi'oduced by the thymus. This thymic factor is probably 

 thymic L.S.F. 



EFFECT OF WHOLE-BODY IRRADIATION ON THYMUS FUNCTION 



The indirect evidence described above suggests that in the initial phase 

 following irradiation, thymic L.S.F. is depressed parallel with the depression 

 in circulating lymphocyte levels. 



In sharp distinction to these initial changes is the situation found in mice 

 showing a lymphocytosis in the second phase following irradiation^. 



L.S.F. assays on mice, 3, 6, 9 and 15 months after whole-body 

 irradiation (250-450 r) have shown that virtually all mice have elevated 

 L.S.F. levels. Such mice also show the apparent development of unre- 

 sponsiveness to stimulation by L.S.F. similar to that previously described in 

 pre-leukaemic and leukaemic AKR and C58 mice^°. However, this apparent 

 unresponsiveness to L.S.F. in irradiated mice has been shown to be a 

 secondary effect of elevated endogenously-produced L.S.F. levels. After 

 thymectomy, irradiated mice show unimpaired responsiveness to stimulation 

 by L.S.F.9 



THYMIC L.S.F. AND LYMPHOID LEUKAEMIA 



The evidence to date^*^ suggests that the normal function of L.S.F. is to 

 stimulate the maturation and/or division of primitive lymphoid cells into 

 mature small lymphocytes. A study of pre-leukaemia arising spontaneously in 

 the high-leukaemia mouse strains AKR and C58 has indicated that such mice 

 invariably show elevated L.S.F. levels and an associated unresponsiveness 

 to stimulation by L.S.F. It has been suggested^*' that this abnormal stimvilus 



27 



