Role of type 1 T helper cells in the resolution of acute Streptococcus pneumoniae sinusitis: a mouse model.
BACKGROUND
We examined the importance of the adaptive and innate immune responses in the resolution of an acute bacterial sinus infection in mice.


METHODS
Recombinase-activating gene knockout (RAG-1(-/-)) (no lymphocytes) and C57BL/6 (wild-type) mice were infected with Streptococcus pneumoniae. For determination of the cell type involved, lymphocytes from mice were adoptively transferred into RAG-1(-/-), C57BL/6 (all lymphocytes), B cell-deficient, and T cell-deficient mice. The degree of infection and inflammation was determined by quantification of S. pneumoniae from nasal lavage and analysis of sinus tissue, respectively.


RESULTS
In C57BL/6 mice, both the infection and inflammation resolved in 21 days, whereas neither resolved in RAG-1(-/-) mice. When C57BL/6 lymphocytes were adoptively transferred into RAG-1(-/-) mice, resolution of the infection and inflammation occurred. Mice without B cells were able to clear the infection, whereas mice without T cells could not clear it. In vitro stimulation of the draining lymph nodes of the infected mice by use of heat-killed S. pneumoniae led to the production of interferon (IFN)- gamma. Flow-cytometric analysis of lymphocytes obtained from sinus mucosa and draining lymph nodes showed an increase in the number of type 1 T helper cell-like cells over that in control mice.


CONCLUSIONS
RAG-1(-/-) mice with innate immunity but no lymphocytes contain--but cannot clear--a bacterial sinus infection. Lymphocytes transferred to RAG-1(-/-) mice clear the infection. The sinus mucosa and draining lymph nodes show an increase in T cells generating IFN- gamma. These data demonstrate that T cells are essential in clearing an acute S. pneumoniae bacterial sinus infection.
Blair
Christopher
C
Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, The University of Chicago, Chicago, IL 60637 , USA.
Naclerio
Robert M
RM
Yu
Xiaohong
X
Thompson
Kenneth
K
Sperling
Anne
A
D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000637:transplantation; D004195:Disease Models, Animal; D016654:Genes, RAG-1; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology* / Q000503:physiopathology; D012852:Sinusitis / Q000276:immunology* / Q000382:microbiology* / Q000503:physiopathology; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology*