TY - JOUR AU - Fontenot, Andrew P. AU - Gharavi, Laia AU - Bennett, Sean R. AU - Canavera, Scott J. AU - Newman, Lee S. AU - Kotzin, Brian L. T1 - CD28 costimulation independence of target organ versus circulating memory antigen-specific CD4+ T cells PY - 2003/09/01/ AB - 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-γ 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI18317 VL - 112 IS - 5 UR - https://doi.org/10.1172/JCI18317 SP - 776 EP - 784 PB - The American Society for Clinical Investigation ER -