CD4+ cytolytic effectors are inefficient in the clearance of Listeria monocytogenes.
Cytotoxic 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-2b beta 2-microglobulin-deficient mice (beta 2M-/-) 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 was found established infection. In beta 2M-/- mice, persistence of L. monocytogenes in the spleen was found preferentially in class II-negative cells. Surprisingly, class I-restricted 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 beta 2M-/- mice. These data strongly suggest that, in the absence of a class I-restricted response, pathogens that elicit a class II-restricted cytotoxic response may escape prompt eradication by the immune system.
Serody
J S
JS
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill 27599-7305, USA.
Poston
R M
RM
Weinstock
D
D
Kurlander
R J
RJ
Frelinger
J A
JA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000276:immunology; D008089:Listeria monocytogenes / Q000302:isolation & purification; D008088:Listeriosis / Q000276:immunology*; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D001613:beta 2-Microglobulin / Q000172:deficiency
D001613:beta 2-Microglobulin; D007371:Interferon-gamma