T-CELL MEMBRANE CD45RA (2H4) AND CD45RO (UCHL1) DETERMINANTS .2. ABERRANT HLA-ABC EXPRESSION BY CD45RA AND CD45RO CELL SUBPOPULATIONS OF MATURE CD4+ T-CELL LEUKEMIAS

Six thymocyte suspensions, 10 normal blood CD4+ CD8- lymphocyte-enriched fractions and leukaemic cells from 24 patients with CD4+ mature T-cell lymphoid malignancy (five Sezary Syndrome, six adult T-cell leukaemia-lymphoma and 13 cases of T-cell prolymphocytic leukaemia) were examined in this study for the expression of membrane HLA-ABC by CD45RA (2H4) and CD45RO (UCHL1) subpopulations. These analyses showed that the main increase in HLA-ABC expression by normal CD4+ CD8- blood lymphocytes (mean 490 to 760 FITC units) paralleled the loss of membrane 2H4 whilst the acquisition of UCHL1 was not associated with any significant change in HLA-ABC staining intensity. The sequence of 2H4 differentiation by normal thymocytes, based on the observed increasing levels of HLA-ABC staining intensity appeared to be (a) CD1a + 2H4- UCHL1+ (25 HLA-ABC fluorescent units), (b)CD1a-2H4intUCHL1+ (134 units), and (c) CD 1a- 2H4 + UCHL1 - (197 units). Quantitative estimates of membrane HLA-ABC expression by leukaemic T-cells revealed marked heterogeneity between individual cases irrespective of diagnostic subgroup. Based on the lower observed limits for normal CD4+ 2H4+ (318 units) and CD4 + 2H4- (478 units) fractions, 14% and 38% respectively of the leukaemic 2H4+ and 2H4- components examined showed reduced HLA-ABC expression. Two cases showed very low membrane HLA-ABC levels that were within the range observed for normal CD1a- thymocytes. In contrast, HLA-ABC staining intensities exceeding that of corresponding normal CD4+ 2H4+ (710 units) and CD4+ 2H4- (1286 units) subpopulations were seen in a high proportion (65% of leukaemic 2H4 + components, with only 14% of 2H4- fractions showing raised levels and, in two cases, these staining intensities exceeded three times the normal observed limits. In addition to the quantitative differences in HLA-ABC expression, a remarkably consistent (81% of evaluable cases) feature of the leukaemic T-cells was that the 2H4-UCHL1+ subpopulation in CD4+ malignancies had a lower HLA-ABC level than the 2H4+UCHL1 subpopulation. This was in marked contrast to normal post-thymic T-cells where increasing HLA-ABC expression was seen with increasing UCHL1 (or decreasing 2H4) staining. These results suggest that leukaemic T-cells have an aberrant intra-thymic and post-thymic sequence of 2H4/UCHL1 expression which has become 'uncoupled' from CD1a/HLA-ABC expression. © 1991 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.