title: CXCR3 and IFN protein-10 in Pneumocystis pneumonia.
abstract: We have previously shown that Tc1 CD8(+) T cells have in vitro and in vivo effector activity against Pneumocystis (PC) infection in mice. Because these cells have preferential expression of CXCR3, we investigated whether CXCR3 was required for host defense activity against PC. Mice deficient in CXCR3 but CD4(+) T cell intact, showed an initial delay but were able to clear the infectious challenge, indicating that CXCR3 signaling is not essential for clearance of PC. CD4-depleted mice had lower levels of monokine induced by IFN-gamma, IFN protein-10 (IP-10), and IFN-inducible T cell alpha-chemoattractant at day 7 of infection and are permissive to PC infection. Overexpression of IP-10 in the lungs by adenoviral gene transfer did not accelerate clearance of infection in control mice but accelerated clearance by day 28 in mice depleted of CD4(+) T cells. This effect was associated with increased recruitment of CD8(+) T to the lungs with higher CXCR3(+) expression levels and enhanced IFN-gamma secretion upon in vitro activation compared with control mice. These results indicate that the CXCR3 chemokines are part of the host defense response to PC, and that IP-10 can direct Tc1 CD8(+) T cell recruitment to the lungs and contribute to host defense against PC even in the absence of CD4(+) T cells.
authors.affiliation: Children's Hospital of Pittsburgh, University of Pittsburgh, Department of Pediatrics, Pittsburgh, PA 15213, USA.
authors.forename: Florencia
authors.initials: F
authors.lastname: McAllister
authors.forename: Sanbao
authors.initials: S
authors.lastname: Ruan
authors.forename: Chad
authors.initials: C
authors.lastname: Steele
authors.forename: Mingquan
authors.initials: M
authors.lastname: Zheng
authors.forename: Laura
authors.initials: L
authors.lastname: McKinley
authors.forename: Lauren
authors.initials: L
authors.lastname: Ulrich
authors.forename: Luis
authors.initials: L
authors.lastname: Marrero
authors.forename: Judd E
authors.initials: JE
authors.lastname: Shellito
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics / Q000502:physiology*; D018014:Gene Transfer Techniques; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008024:Ligands; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D011020:Pneumonia, Pneumocystis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000382:microbiology
chemical_list: D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D008024:Ligands; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma