The B7 adhesion molecule is expressed on activated human T cells: Functional involvement in T‐T cell interactions

Abstract

The B cell antigen B7 delivers a strong co-stimulatory signal for the activation of T cells by binding to its ligands CD28 and CTLA4. Here we demonstrate the surface expression of the B7 molecule on activated human T cells in vitro and under certain conditions in vivo and its functional importance in T-T cell interactions. B7 was detected by flow cytometry on antigen-specific CD4+ and allospecific CD8+ cloned T cells from different donors with anti-B7 monoclonal antibody (mAb) or a soluble CTLA4-C gamma 1 chimera molecule and by reverse transcription-polymerase chain reactions. The expression of B7 was up-regulated following restimulation of the T cell clones and peaked after 7-9 days. Moreover, we show that the B7 molecule on T cells is functionally involved in T-T cell interactions: mAb to CD28 and the CTLA4-Ig fusion protein could inhibit the proliferation of specific T cell clones in response to T cells as antigen-presenting cells (APC) or the proliferation of peripheral blood mononuclear cells in a primary allostimulation with activated T cells as stimulator cells. Finally, we found that B7 can be expressed on freshly isolated circulating T cells since in a preliminary study with a limited number of patients, B7 was present on a subset of CD3+ cells. B7 was expressed on activated T cells (CD4+ and CD8+) of certain human immunodeficiency virus (HIV)-infected individuals (0.5-20% B7+CD8+ cells) or some patients with autoimmune diseases whereas CD3+ cells of healthy individuals did not express B7. The coexpression of major histocompatibility complex class II molecules and B7 may be relevant for the capacity of activated T cells to function as APC. The expression of B7 on T cells in vivo in autoimmune diseases and in HIV infection may be important for a better understanding of these diseases.

Acquisition of CD80 by Human T Cells at Early Stages of Activation: Functional Involvement of CD80 Acquisition in T Cell to T Cell Interaction

“…A previous study by Azuma et al (17) demonstrated that T cell clones coexpress both CD28 and CD80 simultaneously. Similarly, studies by Wyss-Coray et al (34) demonstrated that cloned T cells activated with APCs and rested for various times express CD80 at 7-9 days postactivation. However, it should be pointed out that these T cells were stimulated in the presence of APCs for long period of times.…”

The Number of Responding CD4 T Cells and the Dose of Antigen Conjointly Determine the Th1/Th2 Phenotype by Modulating B7/CD28 Interactions

“…Yet other studies have implicated various costimulatory molecule receptors, such as OX-40 (13,14), ICOS (15), and CD28 (16)(17)(18)(19), in the differential development of Th2 over Th1 cells. Although costimulation is typically considered to be delivered to a T cell by an APC, functional interactions between T cells via costimulatory molecules and their receptors have been described (20); this is especially true for CD28 and the CD80/86 costimulatory molecules (21)(22)(23)(24). Ag dose is also known to affect the Th1/Th2 phenotype of the ensuing response.…”

Insertion of Host-Derived Costimulatory Molecules CD80 (B7.1) and CD86 (B7.2) into Human Immunodeficiency Virus Type 1 Affects the Virus Life Cycle

“…is another mechanism by which CD80/CD86 expression is regulated (21,24,39,43,46,54). For instance, T lymphocytes activated through CD3/CD28 will express both CD80 and CD86 (4,14,48,56). Thus, it will be interesting to investigate the possible relationships between the types of producer cells in which HIV-1 is expanded (e.g., CD4 ϩ T cells versus macrophages), the types of stimuli used to activate virus producer cells, and the degree of incorporation of CD80 and CD86 into mature HIV-1 particles.…”

“…Efficient incorporation of CD80 and CD86 in clinical isolates of HIV-1 produced by cytokine-treated macrophages. As specified above, the two most important cellular reservoirs of HIV-1, i.e., monocytes/macrophages and CD4 ϩ T lymphocytes, can also express both CD80 and CD86 (3,4,14,24,25,48,56). Since CD80 and CD86 are upregulated after the treatment of cells of the monocytic lineage with cytokines (reviewed in reference 28), we finally studied the process of CD80 and CD86 incorporation in field isolates of HIV-1 bearing distinct coreceptor utilization profiles (i.e., R5 and X4).…”

“…For example, the treatment of monocytes with IFN-␥ induces CD80 expression while it upregulates CD86 expression on such cells (14). The coengagement of CD3 and CD28 results in the induction of both CD80 and CD86 on the surfaces of CD4 ϩ T lymphocytes (4,14,48,56). Considering that CD4 ϩ T lymphocytes and monocytes/macrophages constitute major cellular reservoirs of HIV-1 in vivo, it is thus tempting to speculate that HIV-1 can incorporate CD80 and CD86.…”