Primed and unprimed lymphocytes are usually classified as separate sub
sets of cells, based on phenotypic and functional distinctions. In the
case of CD4(+) T lymphocytes, primed cells are thought to proliferate
more vigorously, quickly and easily, and to release a different profi
le of cytokines, than their naive equivalent. However, most of these d
ata were obtained from studies in which populations of lymphocytes wer
e compared before and after antigenic stimulation, and therefore did n
ot distinguish between the effects resulting from the clonal expansion
of specific precursor cells within such populations and those due to
cell differentiation per se. We have investigated the contribution of
precursor cell frequency to some of the functional changes observed in
populations of CD4(+) T cells following antigenic stimulation, using
approaches in which antigen-specific precursor frequencies are high in
both primary and secondary stimulations: mixed leukocyte reaction res
ponses and cells from alpha beta T cell receptor transgenic mice. Our
data suggest that when equivalent: numbers of antigen-specific naive a
nd previously primed CD4(+) responder T cells are compared, there is n
o difference in their potency to proliferate but only the previously a
ctivated subset can generate cytokines such as interferon-gamma.