title: Peripheral blood lymphocyte subset shifts in patients with untreated hematological tumors: evidence for systemic activation of the T cell compartment.
abstract: Flow cytometry immunophenotyping of peripheral blood lymphocyte subsets and multivariate data-analytical techniques revealed that among untreated hemato-oncological patients (n = 48) with lymphomas, acute and chronic myeloid and lymphocytic leukemias, monoclonal gammopathy of undetermined significance, and multiple myeloma, 42% had (nonmalignant) lymphocyte profiles clearly distinct from healthy donors. Notably, a similar pattern of increased CD3+ CD57+, CD3+ HLA-DR+, CD3+ CD(16 + 56)+, CD4- CD8+, CD8+ CD57+, CD8+ CD28-, and CD8+ CD62L- subsets was detected. More extensive three-color immunophenotyping on an additional group of 49 untreated patients revealed that both CD4+ and CD8+ T cells displayed significant increases of activation markers: CD69, CD(16 + 56), HLA-DR, CD71, and CD57, and a loss of CD62L and CD28, which is also interpreted as a sign of activation. Consistent with the phenotypical signs of in vivo immune activation, polyclonal cytolytic activity, measured ex vivo in an anti-CD3-redirected assay, was detected within immunomagnetically purified CD4+ T cells of three out of six B-CLL patients investigated, but not within purified CD4+ T cells of five healthy donors. The purified CD8+ T cells of patients (n = 28) and donors (n = 5) on the other hand displayed similar polyclonal cytotoxic activities at the various effector:target ratios investigated. Tumor-directed cytotoxic activity of purified CD4+ (n = 6) and/or CD8+ T cells (n = 15) against freshly isolated autologous tumor cells was not detected in any of the experiments. Collectively, our results demonstrate systemic T cell activation as a common feature in hematological neoplasia, and a markedly enhanced cytolytic activity of the CD4- subset in CLL patients. The reason(s) for this expansion of activated T cells and its pathophysiologic significance, however, remain unclear.
authors.affiliation: Laboratory of Experimental Hematology, Faculty of Medicine, Catholic University of Leuven, Belgium.
authors.forename: L E
authors.initials: LE
authors.lastname: Van den Hove
authors.forename: P
authors.initials: P
authors.lastname: Vandenberghe
authors.forename: S W
authors.initials: SW
authors.lastname: Van Gool
authors.forename: J L
authors.initials: JL
authors.lastname: Ceuppens
authors.forename: H
authors.initials: H
authors.lastname: Demuynck
authors.forename: G E
authors.initials: GE
authors.lastname: Verhoef
authors.forename: M A
authors.initials: MA
authors.lastname: Boogaerts
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000276:immunology; D019337:Hematologic Neoplasms / Q000097:blood* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology*; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D015703:Antigens, CD