Increased host resistance against Pneumocystis carinii pneumonia in gammadelta T-cell-deficient mice: protective role of gamma interferon and CD8(+) T cells.
Although a clear relationship between alphabeta T-cell receptor-positive (alphabeta-TCR(+)) CD4(+) T cells and susceptibility to Pneumocystis carinii infection exists, the role of other T-cell subsets is less clearly defined. Previous studies have shown that gammadelta-TCR(+) T cells infiltrate into the lung during P. carinii pneumonia. Therefore, the present study examined the role of gammadelta-TCR(+) T cells in host defense against P. carinii pneumonia. C57BL/6 (control) and B6.129P2-Tcrd(tm1Mom) (gammadelta-TCR(+) T-cell-deficient) mice were inoculated intratracheally with P. carinii. At specific time points, mice were sacrificed and analyzed for P. carinii burden, T-cell subsets, and cytokine levels in lung tissue. Analysis of P. carinii burden showed a more rapid and complete resolution of infection in gammadelta-TCR(+) T-cell-deficient mice than in C57BL/6 controls. This augmented resolution was associated with elevated gamma interferon (IFN-gamma) levels in bronchoalveolar lavage fluid predominantly produced by CD8(+) T cells, as well as an increased recruitment of CD8(+) T cells in general. In separate experiments, neutralization of IFN-gamma or depletion of CD8(+) T cells early during infection abolished the augmented resolution previously observed in gammadelta-TCR(+) T-cell-deficient mice. These results show that the presence of gammadelta-TCR(+) T cells modulates host susceptibility to P. carinii pneumonia through interactions with pulmonary CD8(+) T cells and tissue production of IFN-gamma.
Section of Pulmonary and Critical Care and Gene Therapy Program, School of Medicine, Louisiana State University Health Sciences Center, New Orleans 70112, USA.
Chad
C
Steele
Mingquan
M
Zheng
Erana
E
Young
Luis
L
Marrero
Judd E
JE
Shellito
Jay K
JK
Kolls
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009500:Neutralization Tests; D011020:Pneumonia, Pneumocystis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016207:Cytokines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma