Effects of different antigenic microenvironments on the course of CD8⁺ T cell responses in vivo

Abstract

The influence of microenvironment on the course of CD8 + T cell responses in vivo was investigated by injecting H-2Kb-specific T cells from donor TCR transgenic (TCR-Tg) mice into H-2kb-Tg mice. H-2Kb expression in recipients was either ubiquitous (CBK mice) or restricted to myeloid and erythroid cells (K beta mice). Donor T cells proliferated as extensively and acquired similar surface phenotypes in spleen of both recipient types. Thus, neither the restricted pattern of H-2Kb expression nor the significantly reduced level of H-2Kb expression by myeloid cells in Kbeta recipients affects the ability of the splenic microenvironment to prime T cell proliferation in vivo. However, an unsustained burst of cytolytic activity was generated rapidly in spleen of CBK recipients, whereas relatively little cytolytic activity was generated in K beta spleen. This indicates that effector T cells were not generated efficiently in spleen of Kbeta recipients even though extensive T cell proliferation was taking place in this microenvironment. Furthermore, activated donor T cells dispersed rapidly throughout primary and secondary lymphoid organs of Kbeta recipients, whereas few T cells migrated from spleen in CBK recipients. Consequently, the course of CD8+ T cell responses and the anatomical distribution of activated T cells are profoundly influenced by the nature of the antigenic microenvironment encountered in vivo. We conclude that T cells rapidly proliferate and acquire new tissue-homing characteristics but do not differentiate into cytolytic effector cells at the site of priming when they encounter myeloid cells expressing low levels of antigen in vivo.

Evidence for Cooperativity in the Rejection of Cardiac Grafts Mediated by CD4+ TCR Tg T Cells Specific for a Defined Allopeptide

“…Some of these lines fail to reject male skin (5), while others show vigorous responses . In addition, two independent CD8+ TCR Tg mice that directly recognize an MHC class I antigen (the 2C line, a B6 strain TCR Tg specific for H-2L d (9); and the BM3 line, a CBA strain TCR Tg specific for H-2K b (10) have been shown to reject heart allografts. This approach suffers from the potential effector activity of T cells that express endogenously rearranged TCR genes, although treatment of the TCR Tg mice with anti-CD4 mAb has been used to argue that rejection was dependent on the TCR Tg cells (11,12).…”

Cells Expressing Indoleamine 2,3-Dioxygenase Inhibit T Cell Responses

“…CBK transgenic mice express an H-2K b transgene on the inbred CBA strain genetic background (14). BM3 (14) and A1 (15) transgenic mice are TCR-transgenic mice containing large cohorts of H-2K b -specific CD8 ϩ T cells or male (H-Y) Ag-specific CD4 ϩ T cells on the inbred CBA strain genetic background. IDO-transgenic mice were generated by the staff of the Medical College of Georgia Transgenic Unit.…”

“…Splenocytes from TCR transgenic BM3 mice (14) were stained with 1 M CFSE (Molecular Probes, Eugene, OR) in PBS for 35 min at 37°C and washed twice with medium. A total of 10 5 BM3 splenocytes in 100 l/well were used as responders.…”

“…RBCs were removed by osmotic lysis and cells were counted using a Coulter (Seattle, WA) counter. Donor T cells were detected by staining cell preparations with CD4-FITC, CD8-PE, and anti-clonotypic Ab (Ti98 conjugated with biotin) as described previously (14). Stained cells were analyzed by flow cytometry (FACSCalibur; BD Biosciences) using CellQuest analysis software (BD Biosciences).…”

“…BM3 mice contain large cohorts of H-2K bspecific CD8 ϩ T cells (14). After culture for 24 -72 h, cocultures were stained with anti-CD8 mAbs and analyzed by flow cytometry to assess the total number of CD8…”