title: T-Cell Membrane CD45RA (2H4) and CD45RO (UCHL1) Determinants: II, Aberrant HLA-ABC Expression by CD45RA and CD45RO Cell Subpopulations of Mature CD4(+) T-Cell Leukaemias.
abstract: 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(-)2H4(int)UCHL1(+) (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.
authors.affiliation: a Department of Haematology, Cookridge Hospital, Leeds, England.
authors.forename: C S
authors.initials: CS
authors.lastname: Scott
authors.affiliation: a Department of Haematology, Cookridge Hospital, Leeds, England.
authors.forename: S J
authors.initials: SJ
authors.lastname: Richards
authors.affiliation: a Department of Haematology, Cookridge Hospital, Leeds, England.
authors.forename: R A
authors.initials: RA
authors.lastname: Jones
authors.affiliation: b Academic Haematology and Cytogenetics, The Royal Marsden Hospital, London, England.
authors.forename: E
authors.initials: E
authors.lastname: Matutes
authors.affiliation: a Department of Haematology, Cookridge Hospital, Leeds, England.
authors.forename: B E
authors.initials: BE
authors.lastname: Roberts
keywords: CD45RA; Differentiation; HLA-ABC; Leukaemia; T-cells