CD45RO-CELLS IMMUNOREGULATE SPONTANEOUS IN-VITRO IMMUNOGLOBULIN PRODUCTION BY NORMAL AND CHRONIC LYMPHOCYTIC-LEUKEMIA B-CELLS( T)

Immunophenotypic changes in the T-cell compartment in B-CLL are well r ecognised, although the functional significance is less well establish ed. 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. Activat ion 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 CD4 5RO(+) T-cells from alpha CD3-stimulated cultures reduced IgG producti on 3.7-fold, whereas no significant change in IgM production occurred. Supplementing T- and NK-depleted B-cell fractions with purified autol ogous CD45RO(+) T-cells produced a positive correlation between Ig con centration and the CD45RO:CD19 ratio for IgG production but not for Ig M, Collectively, these results suggest that: 1) 'resting' CD45RO(+) (' primed' or memory) T-cells drive mainly the IgG response; 2) activatio n of these T-cells enhances this response; 3) activated CD45RO(+) T-ce lls 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 stimul ation is more typical of regulation by CD45RO(+) T-cells derived from the recent activation of virgin CD45RA(+) T-cells. We believe this cha llenges the view that T-cells in B-CLL are largely memory cells.