CD4(-MONOCYTOGENES() CYTOLYTIC EFFECTORS ARE INEFFICIENT IN THE CLEARANCE OF LISTERIA)

Cytotoxic T lymphocytes (CTL) recognize and lyse target cells through the interaction of the T-cell receptor complex with the class I or cla ss II major histocompatibility complex (MHC). The production of class I-restricted CTL has been shown to be critical to the elimination of s pecific pathogens including Listeria monocytogenes. However, the funct ion of class II-restricted CTL in the clearance of intracellular patho gens is poorly understood. H-2(b) beta(2)-microglobulin-deficient mice (beta(2)M-/-) are not able to produce CD8(+) CTL in response to infec tion with L. monocytogenes. We used this model to evaluate the efficac y of class II-restricted CTL, in the absence of a class I-restricted r esponse, during a primary infection with L. monocytogenes. We demonstr ate that, despite their effectiveness in adoptive transfer of protecti on, Listeria-specific CD4(+) class II-restricted cytotoxic lymphocytes are ineffective in decreasing titres of L. monocytogenes in the splee n after an established infection. In beta(2)M-/- mice, persistence of L. monocytogenes in the spleen was found preferentially in class II-ne gative cells. Surprisingly, class I-restricted CTL from C57BL/6 mice w ere capable of decreasing bacterial titres during an established infec tion even in the absence of detectable class I on the surface of cells from beta(2)M-/- mice. These data strongly suggest that, in the absen ce of a class I-restricted response, pathogens that elicit a class II- restricted cytotoxic response may escape prompt eradication by the imm une system.