I was taught to look for S-phase in DNA cell cycle analysis of peripheral blood when there is a suspicion of viral infection (CD4:CD8 lowered ratio, HLADR expressed on the CD8+/CD3+ population). I've seen the strongest reaction in EBV and CMV infections. T-cells can proliferate via clonal expansion in the peripheral blood.
I've seen some aggressive lymphomas in leukemic phase proliferating in the peripheral blood.
This can only occur in lymphocytes or monocytes unless there is a severe left shift of the granulocytic series. In most cases of mononuclear proliferation, this would occur with a viral infection of some sort.