Interrupting CD28 costimulation before antigen rechallenge affects CD8(+) T-cell expansion and effector functions during secondary response in mice.
The role of CD28-mediated costimulation in secondary CD8(+) T-cell responses remains controversial. Here, we have used two tools - blocking mouse anti-mouse CD28-specific antibodies and inducible CD28-deleting mice - to obtain definitive answers in mice infected with ovalbumin-secreting Listeria monocytogenes. We report that both blockade and global deletion of CD28 reveal its requirement for full clonal expansion and effector functions such as degranulation and IFN-γ production during the secondary immune response. In contrast, cell-intrinsic deletion of CD28 in transferred TCR-transgenic CD8(+) T cells before primary infection leads to impaired clonal expansion but an increase in cells able to express effector functions in both primary and secondary responses. We suggest that the proliferation-impaired CD8(+) T cells respond to CD28-dependent help from their environment by enhanced functional differentiation. Finally, we report that cell-intrinsic deletion of CD28 after the peak of the primary response does not affect the establishment, maintenance, or recall of long-term memory. Thus, if given sufficient time, the progeny of primed CD8(+) T cells adapt to the absence of this costimulator.
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
Monika
M
Fröhlich
Department of Medicine II-Hematology and Medical Oncology, University of Würzburg, Würzburg, Germany.
Tea
T
Gogishvili
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
Daniela
D
Langenhorst
Institute for Multiple Sclerosis Research, Department of Neuroimmunology, Gemeinnützige Hertie-Stiftung and University Medical Centre Göttingen, Göttingen, Germany.
Fred
F
Lühder
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
Thomas
T
Hünig
D000818:Animals; D000941:Antigens / Q000276:immunology*; D001424:Bacterial Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018106:CD28 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
D000941:Antigens; D018106:CD28 Antigens; D018984:Epitopes, T-Lymphocyte
CD28 costimulation; CD8+ T cells; CD8+ T-cell memory; CD8+ effector cell