Chronic primary <i>L. major</i> infection protects against cutaneous Leishmaniasis initiated by infected sand fly challenge; CD4⁺ Th cells transfer protection.

<p>(<b>A and B</b>) Ears of naïve, age matched control mice (Naïve), or mice with a healed but chronic primary infection (Chronic) were exposed to the bites of 6 <i>L. major</i>-infected <i>P. duboscqi</i> sand flies (<i>L.m.</i> Infected SF Challenge, n = 12–16 ears per group). (<b>C and D</b>) Polyclonal TCRβ⁺CD4⁺CD8⁻CD11b⁻NK1.1⁻MHCII⁻ (CD4⁺) or TCRβ⁺CD4⁻CD8⁺CD11b⁻NK1.1⁻MHCII⁻ (CD8⁺) T cells were FACS sorted from 15 chronic mice and independently transferred into 3 wild type naïve recipient mice at their pre-transfer physiological ratios (approximately 1×10⁷ CD4 cells or 8×10⁶ CD8 T cells). One day following transfer, ears were challenged with 5000 <i>L. major</i> metacyclic promastigotes, a dose meant to approximate the number of parasites transmitted by 6 <i>L. major</i>-infected <i>P. duboscqi</i> sand flies (Naïve control group n = 8, Transfer groups n = 6 ears per group). (<b>A and C</b>) Ear lesions were measured weekly in two dimensions and the lesion area determined. <b>In A:</b> (*) p<0.05, Naïve versus chronic; in B: (***) p = 0.0007 versus Naive. (<b>B and D</b>) Parasite loads in individual ears or dLNs at six (B) or three (D) weeks post-challenge. (**) p = 0.0011, (***) p = 0.0003, (****) p<0.0001.