Upregulation of CD4 on CD8(+) T cells: CD4(dim)CD8(bright) T cells constitute an activated phenotype of CD8(+) T cells

Aside from an intermediate stage in thymic T-cell development, the expressi on of CD4 and CD8 is generally thought to be mutually exclusive, associated with helper or cytotoxic T-cell functions, respectively. Stimulation of CD 8(+) T cells, however, induces the de novo expression of CD4. We demonstrat e that while superantigen (staphylococcal enterotoxin B, SEE) and anti-CD3/ CD38 costimulation of purified CD8(+) T cells induced the expression of CD4 on CD8(+) T cells by 30 and 17%, respectively, phytohaemagglutinin (PHA) s timulation did not induce CD4 expression on purified CD8+ T cells but signi ficantly induced the expression of both CD4 on CD8 (CD4(dim)CD8(brigh)t) an d CD8 on CD4 (CD4(bright)CD8(dim))T cells in unfractionated peripheral bloo d mononuclear cells (PBMC). The level of the PHA-mediated induction of CD4( dim)CD8(bright) and CD4(bright)CD8(dim) was at 27 and 17%, respectively. De pletion of CD4(+) T cells from PBMC abrogated this PKA-mediated effect. Aut ologous CD4(+) and CD8(+) T-cell co-cultures in the presence of PHA induced this CD4(dim)CD8(bright) T-cell expression by 33%, demonstrating a role fo r CD4 cells in the PHA-mediated induction of the double positive cells. The induction of CD4(dim)CD8(bright) was independent of a soluble factor(s). P henotypic analysis of CD4(dim)CD8(bright) T cells indicated significantly h igher levels of CD95, CD25, CD38, CD69, CD28, and CD45RO expression than th eir CD8(+)CD4(-) counterparts. CD4(dim)CD8(bright) T cells were also negati ve for CDla expression and were predominately T-cell receptor (TCR) alpha b eta cells. Our data demonstrate that CD4(dim)CD8(bright) T cells are an act ivated phenotype of CD8(+) T cells and suggest: that CD4 upregulation on CD 8(+) T cells may function as an additional marker to identify activated CD8 (+) T cells.