Differential regulation of granzyme and perforin in effector and memory T cells following smallpox immunization.
Primary immunization of healthy adults with vaccinia virus induces a local vesicle or "take" in the majority of vaccinees that previously has been shown to correlate with protection against smallpox. However, the immunologic mechanisms underlying this protective response in humans are not well characterized. We have studied human CD8+ T cells for the expression patterns of phenotypic markers and cytolytic effector molecules before and after primary smallpox immunization using nine-color polychromatic flow cytometry. One month after immunization, vaccinees developed vaccinia virus-specific CD8+ T cells with an effector cell phenotype containing both granzyme A and granzyme B. One year after immunization, we found a significant decrease in granzyme B containing cells and an increased memory cell phenotype in virus-specific CD8+ T cells. Perforin was rarely expressed directly ex vivo, but was highly expressed after Ag-specific activation in vitro. Together, these data suggest an important role for effector CD8+ T cells in controlling poxvirus infection, and have implications for our understanding of human CD8+ T cell differentiation.
Rock
Michael T
MT
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Yoder
Sandra M
SM
Wright
Peter F
PF
Talbot
Thomas R
TR
Edwards
Kathryn M
KM
Crowe
James E
JE
D000328:Adult; D000956:Antigens, Viral / Q000008:administration & dosage; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D005434:Flow Cytometry; D053804:Granzymes; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D054353:Perforin; D010641:Phenotype; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000378:metabolism*; D012900:Smallpox Vaccine / Q000276:immunology / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014616:Vaccinia virus / Q000276:immunology
D000956:Antigens, Viral; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012900:Smallpox Vaccine; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human