title: CD28 costimulation independence of target organ versus circulating memory antigen-specific CD4+ T cells.
abstract: T cell receptor engagement with CD28 costimulation is generally required for naive T cell activation, whereas reactivation of memory cells is less dependent on CD28 costimulation. We studied this process in chronic beryllium disease, in which the frequency of antigen-specific CD4+ T cells in the lung is large and circulating antigen-specific cells are also detectable. In the lung, a large fraction of CD4+ T cells stopped expressing CD28 mRNA and protein, and this change in phenotype correlated with lung inflammation. In the presence of concentrations of CTLA-4Ig that inhibited the CD28-B7 interaction, beryllium-specific CD4+ T cells in lung were still able to proliferate and secrete IFN-gamma in response to beryllium in culture. This functional independence of CD28 costimulation included lung CD28+ effector cells. Although lung CD4+CD28- cells retained the ability to secrete Th1-type cytokines in response to beryllium, they showed less proliferative capacity and were more susceptible to cell death compared with CD28+ T cells. In contrast to lung cells, inhibition of the CD28-B7 interaction markedly reduced responses of beryllium-specific T cells in blood. Taken together, these findings suggest transition within memory CD4+ T cells from CD28 dependence in central memory cells to functional independence and then loss of CD28 expression in effector cells.
authors.affiliation: Department of Medicine,University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. andrew.fontenot@uchsc.edu
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Fontenot
authors.forename: Laia
authors.initials: L
authors.lastname: Gharavi
authors.forename: Sean R
authors.initials: SR
authors.lastname: Bennett
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Canavera
authors.forename: Lee S
authors.initials: LS
authors.lastname: Newman
authors.forename: Brian L
authors.initials: BL
authors.lastname: Kotzin
mesh_terms: D000069594:Abatacept; D017209:Apoptosis; D001607:Berylliosis / Q000276:immunology*; D018106:CD28 Antigens / Q000097:blood / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation
chemical_list: D018106:CD28 Antigens; D018796:Immunoconjugates; D007376:Interleukin-2; D000069594:Abatacept; D007371:Interferon-gamma