@article {542501, title = {PD-L1 and PD-L2 have distinct roles in regulating host immunity to cutaneous leishmaniasis.}, journal = {Eur J Immunol}, volume = {36}, number = {1}, year = {2006}, month = {2006 Jan}, pages = {58-64}, abstract = {To compare the roles of programmed death 1 ligand 1 (PD-L1) and PD-L2 in regulating immunity to infection, we investigated responses of mice lacking PD-L1 or PD-L2 to infection with Leishmania mexicana. PD-L1(-/-) and PD-L2(-/-) mice exhibited distinct disease outcomes following infection with L. mexicana. In comparison to susceptible WT mice, PD-L1(-/-) mice showed resistance to L. mexicana, as demonstrated by reduced growth of cutaneous lesions and parasite burden. In contrast, PD-L2(-/-) mice developed exacerbated disease with increased parasite burden. Host resistance to L. mexicana is partly associated with the development of a Th1 response and down-regulation of the Th2 response. Both PD-L1(-/-) and PD-L2(-/-) mice produced levels of IFN-gamma similar to WT mice. However, the development of IL-4-producing cells was reduced in PD-L1(-/-) mice, demonstrating a role for PD-L1 in regulating Th cell differentiation. This inadequate Th2 response may explain the increased resistance of PD-L1(-/-) mice. Although no alterations in Th1/Th2 skewing were observed in PD-L2(-/-) mice, PD-L2(-/-) mice exhibited a marked increase in L. mexicana-specific antibody production. Increased Leishmania-specific IgG production may suppress the healing response through FcgammaR ligation on macrophages. Taken together, our results demonstrate that PD-L1 and PD-L2 have distinct roles in regulating the immune response to L. mexicana.}, keywords = {Animals, Antigens, CD274, Antigens, CD80, Blotting, Southern, Cell Differentiation, Enzyme-Linked Immunosorbent Assay, Female, Immunoglobulin G, Immunoglobulin M, Leishmania mexicana, Leishmaniasis, Cutaneous, Membrane Glycoproteins, Mice, Mice, Transgenic, Peptides, Programmed Cell Death 1 Ligand 2 Protein, Th1 Cells, Th2 Cells}, issn = {0014-2980}, doi = {10.1002/eji.200535458}, author = {Liang, Spencer C and Greenwald, Rebecca J and Latchman, Yvette E and Rosas, Lucia and Satoskar, Abhay and Freeman, Gordon J and Sharpe, Arlene H} }