Cytotoxic-T-Lymphocyte-Mediated Cytolysis of L Cells Persistently Infected with Chlamydia spp.
STEPHANIE J. RASMUSSEN,1,2* PETER TIMMS,2 P. ROBERT BEATTY,1,3 AND RICHARD S. STEPHENS1,3
1Francis I. Proctor Foundation and Department of Laboratory Medicine, University of California at San Francisco, San Francisco, California 94143-0412
2Centre for Molecular Biotechnology, School of Life Science, Queensland University of Technology, Brisbane, Queensland 4001, Australia
3Program in Infectious Diseases, University of California at Berkeley, Berkeley, California 947203
Persistent chlamydial infections have been proposed as a means whereby chlamydiae evade immune resolution of infection. Such a mechanism would require evasion not only of the humoral immune responses but also of cell-mediated immune responses. We hypothesized that if such a mechanism is important, persistently infected cells should not be recognized by cytotoxic T cells. Persistent infections were simulated in vitro by treatment of Chlamydia trachomatis- or Chlamydia psittaci-infected cells with gamma interferon (IFN-ƴ), penicillin, or tryptophan depletion. Cultures were examined for induction of a chlamydial stress response (measured by transcription of groesl RNA) and for the effects on viability, infectivity, morphology, and immune recognition. Although both IFN-ƴ and penicillin induced aberrant chlamydial morphology and growth, we did not ﬁnd evidence that these treatments elicited a classical stress response. In addition, T-cell-mediated lysis of Chlamydia-infected target cells treated with IFN-g or penicillin or grown in tryptophan-deﬁcient media was examined. The immune cell-mediated lysis of these treated infected cells demonstrated that despite the effects of these compounds on chlamydial growth and development, the infected cells continued to be efﬁciently recognized and killed by cytotoxic T cells. Thus, it seems unlikely that these in vitro models of persistence represent functional mechanisms to evade immune clearance.