Protective immunity and granuloma formation are mediated by two distinct tumor necrosis factor alpha- and gamma interferon-dependent T cell-phagocyte interactions in murine listeriosis: dissociation on the basis of phagocyte adhesion mechanisms.
Listeria-immune mice are able to express protective immunity in the absence of CD4+ T cells and an apparent granulomatous inflammation. Using a monoclonal antibody (5C6) able to inhibit the recruitment of myelomonocytic cells into inflammatory foci by binding to complement receptor type 3 (CR3/CD11b), we could show that protective immunity and granuloma formation indeed depend on two distinct types of T cell-phagocyte interactions. Listeria-specific CD8+ T lymphocytes, possibly in collaboration with CD4- CD8- T cells, rapidly interact with myelomonocytic cells infiltrating infected tissues in a CR3/CD11b-dependent manner. This interaction results in potent antilisterial protection but not in granuloma formation. On the contrary, CD4+ T cells are able to induce adhesion mechanisms that allow the accumulation of monocytes in granulomatous lesions even in the presence of monoclonal antibody 5C6. However, the protective capacity of these CR3/CD11b-independent T cell-mediated immune mechanisms is low in listeriosis. Tumor necrosis factor alpha and gamma interferon, known to be essential for the expression of both resistance and acquired immunity, are shown to be necessarily involved in granuloma formation, too. It therefore remains to be explained why CD8+ T cells, able to secrete both cytokines, do not induce granuloma formation. The data point to the presence of an as yet undefined CD4+ T cell-derived granuloma-inducing factor and favor the hypothesis that CD8+ T cells, in collaboration with circulating phagocytes, mediate immunity by rapidly liberating listeriae from permissive cells or protecting them from becoming infected.
Mielke
M E
ME
Institute of Medical Microbiology and Infectious Diseases Immunology, Freie Universität Berlin, Germany.
Rosen
H
H
Brocke
S
S
Peters
C
C
Hahn
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002450:Cell Communication; D005260:Female; D006099:Granuloma / Q000517:prevention & control*; D007114:Immunization; D007371:Interferon-gamma / Q000502:physiology*; D008088:Listeriosis / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma