title: Reducing the stimulation of CD8+ T cells during infection with intracellular bacteria promotes differentiation primarily into a central (CD62LhighCD44high) subset.
abstract: During infection with lymphocytic choriomeningitis virus, CD8(+) T cells differentiate rapidly into effectors (CD62L(low)CD44(high)) that differentiate further into the central memory phenotype (CD62L(high)CD44(high)) gradually. To evaluate whether this CD8(+) T cell differentiation program operates in all infection models, we evaluated CD8(+) T cell differentiation during infection of mice with recombinant intracellular bacteria, Listeria monocytogenes (LM) and Mycobacterium bovis (BCG), expressing OVA. We report that CD8(+) T cells primed during infection with the attenuated pathogen BCG-OVA differentiated primarily into the central subset that correlated to reduced attrition of the primed cells subsequently. CD8(+) T cells induced by LM-OVA also differentiated into central phenotype cells first, but the cells rapidly converted into effectors in contrast to BCG-OVA. Memory CD8(+) T cells induced by both LM-OVA as well as BCG-OVA were functional in that they produced cytokines and proliferated extensively in response to antigenic stimulation after adoptive transfer. During LM-OVA infection, if CD8(+) T cells were guided to compete for access to APCs, then they received reduced stimulation that was associated with increased differentiation into the central subset and reduced attrition subsequently. Similar effect was observed when CD8(+) T cells encountered APCs selectively during the waning phase of LM-OVA infection. Taken together, our results indicate that the potency of the pathogen can influence the differentiation and fate of CD8(+) T cells enormously, and the extent of attrition of primed CD8(+) T cells correlates inversely to the early differentiation of CD8(+) T cells primarily into the central CD8(+) T cell subset.
authors.affiliation: Laboratory of Cellular Immunology, Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada.
authors.forename: Henk
authors.initials: H
authors.lastname: van Faassen
authors.forename: Marsha
authors.initials: M
authors.lastname: Saldanha
authors.forename: Deanna
authors.initials: D
authors.lastname: Gilbertson
authors.forename: Renu
authors.initials: R
authors.lastname: Dudani
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Krishnan
authors.forename: Subash
authors.initials: S
authors.lastname: Sad
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004527:Egg Proteins / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology*; D019041:L-Selectin / Q000096:biosynthesis*; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D004527:Egg Proteins; D018960:Hyaluronan Receptors; C110366:OVA-8; D010446:Peptide Fragments; D014613:Vaccines, Attenuated; D019041:L-Selectin; D010047:Ovalbumin