Julia G. Johnson

Use of adoptive transfer of T-cell-antigen-receptor-transgenic T cells for the study of T-cell activation in vivo

Summary: Adoptive transfer of TCR‐transgenic T cells uniformly expressing an identifiable TCR of known peptide/MHC specificity can be used to monitor the in vivo behavior of antigen‐specific T cells. We have used this system to show that naive T cells are initially activated within the T‐cell zones of secondary lymphoid tissue to prohferate in a B7‐dependent manner. If adjuvants or inflammatory cytokines are present during this period, enhanced numbers of T cells accumulate, migrate into B‐cell‐rich follicles, and acquire the capacity to produce IFN‐7 and help B cells produce IgG2a. If inflammation is absent, most of the initially activated antigen‐specific T cells disappear without entering the follicles and the survivors are poor producers of IL‐2 and IFN‐γ Our results indicate that inflammatory mediators play a key role in regulating the anatomic location, clonal expansion, survival and lymphokine production potential of antigen‐stimulated T cells in vivo.

Accessory cell-derived signals required for T cell activation

Various populations of accessory cells differ in their abilities to function as effective antigen-presenting cells (APC) and stimulate CD4+ T cells to produce interleukin-2. Three important factors directly related to APC potency are the expression of class II major histocompatibility complex molecules and the ability to present peptide antigens to the T cell antigen receptor, the expression of costimulatory ligands which deliver important activation signals independent of T cell receptor occupancy and the expression of adhesion molecules which promote conjugate formation so that these activation signals can be effectively delivered to the T cells. The relative importance of these accessory cell functions in T cell activation will be discussed, with an emphasis on costimulation and the CD28/B7 receptor/ligand pair. The consequence of inadequate costimulation by an otherwise effective APC in inducting T cell anergy will also be discussed. *** DIRECT SUPPORT *** A02GS021 00006

Costimulating Factors and Signals Relevant for Antigen Presenting Cell Function

The antigen-specific activation of CD4+ T lymphocytes is absolutely dependent on ligands expressed on the surface of specialized hematopoietic cells1 known as antigenpresenting cells (APC). Recent results from many laboratories suggest that these ligands include: major histocompatibility complex (MHC) -encoded class II molecules that are important for presenting antigenic peptides to the T cell antigen receptor (TCR); adhesion molecules that facilitate the formation of T cell/APC conjugates; and molecules that transduce nonspecific costimulatory signals upon binding their complementary T cell receptors1-3. The efficiency of various APC types in their capacity to stimulate T cells can therefore be influenced by qualitative and/or quantitative differences in the expression or function of any of these molecules. Here we describe our analysis of the contribution of antigen-presentation, adhesion, and costimulation to the functional APC potency of dendritic cells and B cells.