Con A-induced suppressor cell function depends on the activation of the CD4+CD45RA inducer T cell subpopulation

Human T cells incubated for 48 hr with Con A suppress B cell Ig production. We sought to define the interactions between CD4+ T cells and CD8+ T cells in the generation of suppressor cell activity following Con A stimulation. Con A-activated CD4+ inducer T cells suppressed Ig production in autologous cocultures of T cells and B cells by 84%, while PHA-activated CD4+ T cells could not. However, Con A-activated CD4+ T cells are not themselves suppressors. When Con A-activated CD4+ T cells were added to coculture of B cells plus T cells depleted of CD8+ T cells, no suppression of Ig production was observed. Furthermore, these Con A-activated CD4+ T cells were able to provide excellent help for Ig production. Therefore, Con A-induced suppressor cell function requires a CD4+ suppressor/inducer acting on a CD8+ suppressor/effector ultimately resulting in the down regulation of B cell Ig synthesis. Human CD4+ inducer T cells can be functionally dissected into helper/inducer or suppressor/inducer T lymphocytes based on their expression of either the CDw29 or CD45RA surface molecules, respectively. Following incubation with Con A the expression of CD45RA on CD4+ T cells increased from 34 to 80% (P = 0.001) while CDw29 expression was unchanged. Incubating lymphocytes with PHA resulted in a non-specific increase in both CD45RA and CDw29 expression by CD4+ T cells. The increase in CD4+CD45RA expression was a result of active proliferation by the Con A-stimulated T cells. Suppression of Ig secretion was directly correlated with the enhanced CD45RA expression following Con A activation. We demonstrate that enhanced suppressor/inducer function is unique to Con A stimulation and was not observed following activation by PHA. Furthermore, short-term culture with Con A results in the selective expansion of the CD4+CD45RA T cell subpopulation.