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T Cytotoxic-1 CD8⁺ T Cells Are Effector Cells against Pneumocystis in Mice¹

Florencia Mc Allister^*, Chad Steele^*, Mingquan Zheng^*, Erana Young, Judd E. Shellito, Luis Marrero and Jay K. Kolls^2,*

^* Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15213; and Gene Therapy Program, Louisiana State University Health Sciences Center, School of Medicine, New Orleans, LA 70112

Host defenses are profoundly compromised in HIV-infected hosts due to progressive depletion of CD4⁺ T lymphocytes. A hallmark of HIV infection is Pneumocystis carinii (PC) pneumonia. Recently, CD8⁺ T cells, which are recruited to the lung in large numbers in response to PC infection, have been associated with some level of host defense as well as contributing to lung injury in BALB/c mice. In this study, we show that CD8⁺ T cells that have a T cytotoxic-1 response to PC in BALB/c mice, as determined by secretion of IFN-, have in vitro killing activity against PC and effect clearance of the organism in adoptive transfer studies. Moreover, non-T cytotoxic-1 CD8⁺ T cells lacked in vitro effector activity and contributed to lung injury upon adoptive transfer. This dichotomous response in CD8⁺ T cell response may in part explain the clinical heterogeneity in the severity of PC pneumonia.

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