Mycobacterium bovis BCG-infected mice are more susceptible to staphylococcal enterotoxin B-mediated toxic shock than uninfected mice despite reduced in vitro splenocyte responses to superantigens.
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.
Laboratory of Cellular Immunology, Institute for the Biological Sciences, National Research Council, Ottawa, Ontario, Canada.
João A
JA
Pedras-Vasconcelos
Yvan
Y
Chapdelaine
Renu
R
Dudani
Henk
H
van Faassen
Dean K
DK
Smith
Subash
S
Sad
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D005260:Female; D018960:Hyaluronan Receptors; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology*; D012772:Shock, Septic / Q000150:complications / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D014376:Tuberculosis / Q000150:complications / Q000276:immunology*
D004768:Enterotoxins; D018960:Hyaluronan Receptors; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma