THE RADIATION-SENSITIVE COSTIMULATORY FACTORS INVOLVED IN B-CELL-DEPENDENT T-CELL ACTIVATION BY MINOR LYMPHOCYTE STIMULATING ANTIGEN

The regulation of CD28/B7 is important in T-cell activation. It has be en argued that its aberrant expression is involved in the radiosensiti vity of B-cell-stimulated T-cell response. Here, this possibility is s tudied in the mixed lymphocyte reaction (MLR)induced by minor lymphocy te-stimulating (Mls) antigen-presenting irradiated B cells, By using a nti-CD28 antibody, the CD28/B7-2-, LFA-1/ICAM-1-dependent Mls-MLR was found to be restored, By flow cytometry, approximately 70% B cells wer e lost but with unaffected B7-2 expression, indicating that the modera te CD28 costimulation was caused by mortality of antigen presenting ce lls. Despite of costimulatory deficiency, T cells were shown primed. H owever, the expression of early activation markers CD25 and CD69, whic h was shown unaffected by B7/CD28 blocking, was found partially inhibi ted. To further understand the regulation, we examined the ICAM-1 expr ession, and found that it was again not altered on irradiated B cells. Thus, the radiation-induced rapid loss of resting B cells may be the basic mechanism causing insufficient costimulatory activity in radiose nsitive B-T interaction. Furthermore, the presence of an element, othe r than B7-2, involving in controlling early T-cell response is suggest ed.