Thymus-dependent memory phenotype CD8 T cells in naive B6.H-2Kb-/-Db-/- animals mediate an antigen-specific response against Listeria monocytogenes.
B6.H-2Kb-/-Db-/- (DKO) mice have greatly reduced numbers of mature CD8alphabeta T cells in their periphery. However, these non-class Ia-selected CD8alphabeta T cells are able to mediate immune responses to a number of pathogens. Approximately 60% of the CD8alphabeta T cells in the spleen and peripheral lymph nodes of naive DKO mice display a memory (CD44high) phenotype. To investigate the origins of these non-class Ia-selected CD8alphabetaCD44high cells, we traced the phenotype of recent thymic emigrants and found that most were CD44low. We also determined whether their appearance was thymus dependent and found that only a small percentage of non-class Ia-selected CD8alphabetaCD44high cells develop in a thymus-independent pathway. Functionally, CD8alphabetaCD44high cells from DKO mice are able to secrete IFN-gamma in response to IL-12 and IL-18 in the absence of cognate Ag. When challenged with anti-CD3 in vivo, nearly half of these cells produce IFN-gamma within 3 h. When purified CD8alphabetaCD44high cells from Thy1.2.DKO mice were transferred into Thy1.1 DKO recipients and then challenged with Listeria monocytogenes, an Ag-specific anti-L. monocytogenes response was observed 6 days later. Our data suggest that non-class Ia-selected CD8alphabetaCD44high cells in naive animals can respond rapidly to Ag and play a role in the innate as well as the early phase of the acquired immune response.
Su
Jie
J
Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Berg
Rance E
RE
Murray
Sean
S
Forman
James
J
D000818:Animals; D000942:Antigens, Bacterial; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002678:Chimera / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D018960:Hyaluronan Receptors / Q000378:metabolism; D007113:Immunity, Innate; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008089:Listeria monocytogenes / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000942:Antigens, Bacterial; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D018960:Hyaluronan Receptors