Function and differentiation of CD4+ subsets identified by the monoclonal antibodies WR16 and WR19

Nesbitt, Andrew Malcolm (1990) Function and differentiation of CD4+ subsets identified by the monoclonal antibodies WR16 and WR19. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

The monoclonal antibodies WR16 and WR19 were used to isolate two reciprocal subsets of CD4⁺ lymphocytes by negative selection using either magnetic beads or the panning technique. WR15 was found to bind the 220 KD and 205 KD isoforms of the leucocyte common antigen by immunoprecipitation and by western blotting. The CD4⁺WR16^-WR19⁺ subset exhibited helper inducer activity in a PWM driven Ig assay and did not produce IL2 when stimulated with PHA whereas the CD4⁺WR16⁺WR19^- subset had a greater proliferative response in the presence of mitogen as measured by tritiated thymidine incorporation whereas the CD4⁺WR16^-WR19⁺ subset had a greater response in the presence of IL2 and soluble antigens. The phenotype of IL2 dependent CD4⁺ clones was predominantly WR16^-WR19⁺. Culture of the CD4⁺WR16⁺WR19^- lymphocytes with PHA or PPD induced a phenotypic change resulting in a population which was WR16^-WR19⁺. Investigation of the functional activity before and after activation indicated that the change in phenotype correlated with a functional conversion from suppressor to helper inducer activity and also a reduction in the level of IL2 production. These results suggest that the CD4⁺WR16⁺WR19^- suppressor subset comprises cells that differentiate to WR16^-WR19⁺ helper inducer cells after exposure to antigen or mitogen.