CD45RO+ T-cells immunoregulate spontaneous in vitro immunoglobulin production by normal and chronic lymphocytic leukaemia B-cells

Abstract

Immunophenotypic changes in the T-cell compartment in B-CLL are well recognised, although the functional significance is less well established. In this study we examined the immunoregulatory capacity of CD45RO+ T-cells to modulate in vitro IgG and IgM production by B-CLL cells in comparison to normal PB B-cells. Removal of CD45RO+ T-cells from normal PB lymphocyte cultures was associated with a 2.3-fold reduction in IgM production and a 7.9-fold reduction in IgG production. Activation of the T-cell component by alpha CD3 stimulation enhanced IgG and IgM production by factors of 1.85 and 3.4 respectively. Removal of CD45RO+ T-cells from alpha CD3-stimulated cultures reduced IgG production 3.7-fold, whereas no significant change in IgM production occurred. Supplementing T- and NK-depleted B-cell fractions with purified autologous CD45RO+ T-cells produced a positive correlation between Ig concentration and the CD45RO:CD19 ratio for IgG production but not for IgM. Collectively, these results suggest that: 1) 'resting' CD45RO+ ('primed' or memory) T-cells drive mainly the IgG response; 2) activation of these T-cells enhances this response; 3) activated CD45RO+ T-cells derived from the recent transformation of the CD45RA+ ('virgin' or naive) population drives mainly the IgM response. In B-CLL cultures however, the pattern of Ig production in response to alpha CD3 stimulation is more typical of regulation by CD45RO+ T-cells derived from the recent activation of virgin CD45RA+ T-cells. We believe this challenges the view that T-cells in B-CLL are largely memory cells.