We wonder, for the better part of A Tale of Two Cities, why Madame Defarge seems so angry and so intent on punishing Charles Darnay--and later his entire family. When the Defarges are part of the storming of the Bastille, they go immediately to Dr. Manette's former cell (one hundred five north tower) and conduct a systematic search. What they found, we discover later, is the evidence which incriminates Charles and his entire family as part of the hated French aristocracy.
The letter was written by Dr. Manette while he was in prison and recounts the story of his imprisonment at the hands of Charles's father and uncle, Monsieur the Marquis (twin brothers). The story is tragic.
The two Evremonde brothers were cruel and sadistic, representing all the worst of the aristocratic class. What they wanted they got--and they wanted a young married woman in their village. They took her, and in doing so humiliated her husband to death, killed her brother in a duel, and caused her father to have a heart attack which killed him. In an unexpected act of charity toward their victims, the men virtually kidnapped the young Dr. Manette, who did his best to save the two who were alive when he got there--the young girl and her brother. He heard enough of their story before they died to be dangerous to the brothers. They returned him to his home, but their spies intercepted a letter written by Dr. Manette explaining to the authorities what he had witnessed. These Evremonde brothers could not allow that, so they used their influence with the Court to have him imprisoned.
It's a tragic story, though we know beyond question that Charles has not carried on this horrible Evremonde legacy. What makes this important to Madame Defarge is that it's her family about which this letter was written. Her father, brother, brother-in-law, and sister all died at the hands of this family--which explains her thirst for vengeance against any heirs. The letter ends with Dr. Manette's curse of condemnation on the family for all generations, which makes him the prime witness against his own son-in-law. Madame Defarge will not be content until the entire family has been killed, just as they killed her family. It's probably a good thing she dies before they all manage to escape with their lives.