title: Naive CD28-deficient T cells can initiate but not sustain an in vitro antigen-specific immune response.
abstract: Naive T cells require an Ag-specific signal, as well as a costimulatory signal to mount a primary Ag-specific response. Because of their low precursor frequency, it has been difficult to study costimulatory requirements of these Ag-specific T cells. We have generated a CD28-deficient mouse that has been bred to a TCR transgenic (Tg) mouse to better study the function of CD28 during CD4+ T cell responses to Ag. In the absence of CD28, naive TCR Tg T cells responded vigorously to peptide, but responded poorly to mitogen activation. Comparison of activation-induced cell-surface molecules, including CD25, CD44, CD69, and CD71, showed no significant differences between CD28+ and CD28- TCR Tg T cells during the first 24 to 48 h after Ag stimulation. Despite relatively normal surface phenotype and normal proliferative response to Ag, CD28- T cells produced little IL-2, had a decreased sensitivity to lower Ag concentrations, and were unable to maintain their proliferative response. These results suggest that naive T cells are able to utilize other costimulatory signals to initiate a primary Ag-specific response, but require CD28 for optimal, sustained proliferation.
authors.affiliation: Howard Hughes Medical Institute, Washington School of Medicine, St. Louis, MO 63110, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Lucas
authors.forename: I
authors.initials: I
authors.lastname: Negishi
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: L E
authors.initials: LE
authors.lastname: Fields
authors.forename: D Y
authors.initials: DY
authors.lastname: Loh
mesh_terms: D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000276:immunology; D001483:Base Sequence; D018106:CD28 Antigens / Q000235:genetics* / Q000502:physiology*; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D005434:Flow Cytometry; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007376:Interleukin-2; D015847:Interleukin-4; D000069594:Abatacept