Failure of CD1D-/- mice to elicit hypersensitive granulomas to mycobacterial cord factor trehalose 6,6'-dimycolate.

The present study defines pathologic differences in acute and hypersensitive responses to Mycobacterium tuberculosis glycolipid trehalose-6,6′-dimycolate (TDM, cord factor) in normal BALB/c mice and those deficient in group II CD1 molecule CD1d1. Mice immunized against TDM demonstrate hypersensitive responses, yet the mechanisms for TDM presentation remain elusive. Mice lacking CD1d (CD1D-/-) demonstrate dysregulated granulomatous response to TDM, compared with CD1D+/- heterozygous controls. Because CD1d-restricted T cells can regulate macrophage immune functions at mucosal surfaces, we hypothesized that CD1D-/- mice would show deficient TDM-induced hypersensitive pulmonary granulomatous response in which T cells play a central role. Control CD1D+/+ mice sensitized and subsequently challenged with TDM demonstrated aggressive inflammation defined by monocytic lesions contained by CD3+ lymphocytic cuffing. CD1D-/- mice demonstrated distinctly different pathologies, with edema present concurrent with extende...