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Apparent requirement for CD4+ T cells in primary anti-herpes simplex virus cytotoxic T-lymphocyte induction can be overcome by optimal antigen presentation.

Mice depleted in vivo of either CD4+ or CD8+ T cells were used to define the requirement for interaction between the two T subsets for the induction and maturation of a herpes simplex virus (HSV) cytotoxic T-lymphocyte (CTL) response. Whereas C3H mice generated normal CD8+ CTL in the absence of CD4+ T cells, responses were undetectable in BALB/c mice. However, the role of CD4+ T cells appeared to be to supply helper factors for CTL maturation, as the numbers of CTL precursors in CD4-depleted mice were similar to those in nondepleted animals. Moreover, CTL responses were demonstrable if CD4-depleted primed populations were stimulated with antigen or supplied with a source of helper factors. The optimal means of presenting antigen appeared to be via dendritic cells. Our results indicated that CD8+ cells alone were fully capable of differentiating into CTL provided they were appropriately stimulated with antigen. Possibly, the environment necessary for this to occur in vivo is usually lacking, accounting for the fact that in the mouse, it usually is not possible to demonstrate HSV-specific CTL unless cells are cultured or restimulated in vitro.