Abstract |
Type 1 T-cell responses against intracellular pathogens play a crucial role in mediating protection. We examined whether the induction of a strong type 1 T-cell response during a chronic bacterial infection influences responses to superantigens capable of inducing acute shock. Intravenous infection of mice with Mycobacterium bovis BCG appeared to induce a progressive anergy towards staphylococcal enterotoxin B (SEB) and towards antigen preparation of BCG (BCG-Ag) itself, based on diminished gamma interferon (IFN-gamma) production by SEB- and BCG-Ag-stimulated splenocytes from infected mice. In contrast to these in vitro results, injection of SEB into BCG-infected mice led to a dramatic increase in the serum IFN-gamma levels and the death of infected but not of control mice. In vitro hyporesponsiveness towards SEB and BCG-Ag occurred only with unfractionated splenocyte cultures, as purified T cells from infected mice produced higher levels of IFN-gamma. Hyporesponsiveness towards SEB and BCG-Ag in unfractionated splenocyte cultures was not due to suppressive antigen-presenting cells (APCs), as APCs from infected mice stimulated higher levels of IFN-gamma from purified T cells. The diminished IFN-gamma levels observed with bulk splenocytes appear to be due to changes in the T-cell-to-APC ratio that result in a decreased proportion of T cells, coupled to reduced proliferative responses and an increased susceptibility of effector T cells to activation-induced cell death in vitro. Our results indicate that the reported phenomena of T-cell anergy during mycobacterial infection may be an in vitro consequence of the development of a strong type 1 response in vivo.
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Authors | João A Pedras-Vasconcelos, Yvan Chapdelaine, Renu Dudani, Henk van Faassen, Dean K Smith, Subash Sad |
Journal | Infection and immunity
(Infect Immun)
Vol. 70
Issue 8
Pg. 4148-57
(Aug 2002)
ISSN: 0019-9567 [Print] United States |
PMID | 12117923
(Publication Type: Journal Article)
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Chemical References |
- Enterotoxins
- Hyaluronan Receptors
- Superantigens
- enterotoxin B, staphylococcal
- Interferon-gamma
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Topics |
- Animals
- Antigen-Presenting Cells
(immunology)
- CD4-Positive T-Lymphocytes
(cytology, immunology)
- CD8-Positive T-Lymphocytes
(immunology)
- Cells, Cultured
- Disease Susceptibility
(immunology)
- Enterotoxins
(immunology)
- Female
- Hyaluronan Receptors
- Interferon-gamma
(biosynthesis)
- Mice
- Mice, Inbred BALB C
- Mycobacterium bovis
(immunology)
- Shock, Septic
(complications, immunology)
- Spleen
(cytology, immunology)
- Staphylococcus aureus
(immunology)
- Superantigens
(immunology)
- Tuberculosis
(complications, immunology)
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