Acquisition of CD80 (B7-1) by T Cells

Abstract

Activation of T cells usually requires two signals. Signal 1 is mediated via a peptide-MHC on the APC; signal 2 is mediated via a costimulatory molecule on the APC surface. We demonstrate here that naive CD4+ T cells actually acquire the costimulatory molecule CD80 (B7-1) from syngeneic APCs after activation. This phenomenon was demonstrated showing acquisition of CD80 by T cells from CD80/CD86 (B7-2) knockout mice, and by treating T cells with cyclohexamide to further rule out endogenous expression of CD80 by T cells. Moreover, no CD80 mRNA could be detected in T cells that had acquired CD80. The amount of acquisition of CD80 by T cells was shown to be directly related to both the strength of signal 1 and the amount of CD80 on the APC. Specificity of this acquisition was also shown by the lack of acquisition by T cells from CD28 knockout mice (implicating CD28 in this process), the lack of acquisition of CD40 (another molecule on the APC surface) by T cells, and confocal microscopy studies. We demonstrate for the first time that 1) naive T cells, following acquisition of CD80 from APCs, were themselves shown to be capable of acting as APCs; and 2) memory T cells that have acquired CD80 from APCs undergo apoptosis in the presence of increased levels of signal 1. Thus we demonstrate both immunostimulatory and immunoregulatory functions as a result of CD80 acquisition by different T cell populations.

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

“…Previously, it was reported that T cell-APC contact is followed by a down-regulation of TCR (25,26) and that T cell-APC interaction can cause APC-derived surface molecules to adhere to the surface of T cells (27,28). Recently, our laboratory as well as others have demonstrated the acquisition of CD80 molecules by naive and memory murine CD4 ϩ T cells via direct transfer of these molecules at the site of interaction through CD28 receptors (10,12). We further demonstrated that upon acquisition of CD80, CD4 ϩ T cells from mice could act as an APC to stimulate other T cells, thus amplifying an immune response.…”

“…However, it should be mentioned that using fusion proteins to block the CD80 on APCs might lead to steric hindrance that interferes with cell:cell conjugate formation; this might also contribute to the inhibition of CD80 acquisition by T cells. However, it should be pointed out that previously reported (12) murine studies demonstrated that CD28 is responsible for CD80 acquisition. In addition, the results of proliferation assays demonstrated that CD4 ϩ T cells, upon acquisition of CD80, can further stimulate themselves and neighboring T cells to proliferate.…”

“…In our previous studies, we had demonstrated that high affinity TCR-transgenic murine T cells were able to acquire CD80 (12). In this study, for the first time, we demonstrated that naive human a C1R-A2 cells were pretreated with 30 g/ml CTLA-4 Ig fusion protein or CD28 Ig fusion protein as described in Materials and Methods, and then were cocultured with purified human CD4 ϩ T cells in the presence of 1 g/ml anti-CD3.…”

“…Recently, studies in mouse systems demonstrated that T cell-APC interaction can cause APC-derived surface molecules to adhere to the surface of T cells and to be internalized through TCR endocytosis (10,11). Moreover, data from our laboratory and others in mouse models demonstrated that CD80 molecules are physically acquired by naive as well as memory T cells from APCs shortly after T cell activation; this acquisition plays a role in the activation of bystander T cells (12). In the early 1970s, Hudson et al (13,14) also demonstrated that alloreactive murine T blast cells generated during a graft-vs-host reaction in vivo expressed Ig molecules.…”

T cell activation correlates with an increasedproportion of antigen among the materials acquiredfrom target cells

“…The identity of the molecules acquired differs according to the target cell type [14][15][16], and mainly concerns plasma membrane molecules [4, 10,14]. Transfer via trogocytosis has clearly been shown to occur for MHC [16][17][18][19][20][21][22] and co-stimulatory molecules [16,18,19,[23][24][25], virus receptors [26], adhesion molecules [18][19][20] and lipids [4,10,15,16,26,27]. Trogocytosis has been recorded with every lymphocyte type, and its proposed role(s) differ depending on the cell type.…”