CD4⁺ cytolytic effectors are inefficient in the clearance of Listeria monocytogenes

Abstract

SUMMARYCytotoxic T lymphocytes (CTL) recognize and lyse target cells through the interaction of the T-cell receptor complex with the class I or class II major histocompatibility complex (MHC). The production of class I-restricted CTL has been shown to be critical to the elimination of specific pathogens including Listeria monocytogenes. However, the function of class II-restricted CTL in the clearance of intracellular pathogens is poorly understood. H-2 b b2 -microglobulin-deficient mice (b 2 Mÿ/ÿ) are not able to produce CD8 CTL in response to infection with L. monocytogenes. We used this model to evaluate the efficacy of class II-restricted CTL, in the absence of a class I-restricted response, during a primary infection with L. monocytogenes. We demonstrate that, despite their effectiveness in adoptive transfer of protection, Listeria-specific CD4 class II-restricted cytotoxic lymphocytes are ineffective in decreasing titres of L. monocytogenes in the spleen after an established infection. In b 2 Mÿ/ÿ mice, persistence of L. monocytogenes in the spleen was found preferentially in class II-negative cells. Surprisingly, class Irestricted CTL from C57BL/6 mice were capable of decreasing bacterial titres during an established infection even in the absence of detectable class I on the surface of cells from b 2 Mÿ/ÿ mice. These data strongly suggest that, in the absence of a class I-restricted response, pathogens that elicit a class IIrestricted cytotoxic response may escape prompt eradication by the immune system.

High Efficiency of Antiviral CD4+ Killer T Cells

“…Though their overall CTL activity appeared relatively small, L. monocytogenes- specific CD4 + T cells in fact killed with an efficiency comparable to LCMV-specific CD4 + CTL considering that the latter population is 3–4 times larger (not shown). To be sure, the capacity of LM-specific CD4 + T cells for target cell killing has been noted before, but these early studies were limited to the use of CD4 + T cell lines and clones generated in vitro from LM-infected donor mice [51], [52]. To our knowledge, only one other report has investigated the in vivo cytolytic function of antibacterial CD4 + T cells; conducted during the acute phase of a Mycobacterium tuberculosis (Mtb) challenge, this study also distinguished itself by providing one of the very few side-by-side comparisons of in vivo CD4 + and CD8 + CTL activities [53].…”

Cytokines in the induction and expression of T‐cell‐mediated granuloma formation and protection in the murine model of listeriosis

“…74). only CD8* T cells have been convincingly shown to do so in vivo (64, [75][76][77][78]. Conversely, all L. monocytogenes-induced T-cell subpopulations have been shown to produce IFN-y in vitro, but little is known about the cytokines produced by these T-cell subsets in vivo.…”