CD4+ T Cells: Specificity and Function

Janeway, Charles A.; Carding, Simon R.; Jones, Barry; Murray, Joseph S.; Portolés, Pilar; Rasmussen, Robert A.; Rojo, José María; Saizawa, Kaj; West, Jeffrey; Bottomly, Kim

doi:10.1111/j.1600-065x.1988.tb00732.x

Cited by 260 publications

(100 citation statements)

References 100 publications

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“…The latter is known not to depend upon a CD4-CD3/TcR interaction [15]. The present results are, thus, compatible with the hypo thesis that CD4 ligands and putative CD4 ligands (gpl60 and MHC class II-derived peptides) can inhibit through negative signaling of both activated and resting T cell adhesion ( [6,33,34]; Mazerolles et aL, Hum. Immunol., in press).…”

Section: Discussionsupporting

confidence: 90%

Regulation of LFA‐1‐mediated T cell adhesion by CD4

et al. 1991

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Heterotypic adhesion of T lymphocytes to monocytes, B lymphocytes, or other target cells is mainly mediated by LFA-1 and CD 2 molecules. Low-affinity binding of restingTcells can be transiently up-regulated by cross-linking of CD3. We have previously found that binding of specific ligands to CD4 can down-regulate adhesion of resting T cells to B cells. We now show that the enhanced adhesiveness of CD4+ T cells induced by CD3 cross-linking using plastic-bound anti-CD3 antibody can also be inhibited by several CD4 ligands, i.e. anti-CD4 antibodies, the gpl60 env protein of human immunodeficiency virus, as well as by putative CD4 ligands, i.e. synthetic peptides analogous to the gp 160-binding site to CD4 (positions 418-434 and 449-464) and a 12-mer synthetic peptide (DR-12) analogous to positions 35-46 of HLA class II |3 subunit and including the highly conserved Arg-Phe-Asp-Ser (RFDS) sequence» After CD3 cross-linking, maximal binding of Tcells to HLA class II-positive and -negative B cells was similar, although binding to HLA class II-negative B cells was more prolonged.Tcells that were passively induced to up-regulate adhesion by binding of a CD 1 la-specific antibody, NKIL16, known to enhance LFA-1-dependent adhesiveness, were less sensitive to the inhibitory effect of the DR-12 peptide, whereas the inhibitory effects of gpl60 were preserved. The kinetics of adhesion of NKIL16-pretreated T cells was not influenced by LILA class II expression at the B cell surface. Together, these results strongly suggest that CD4-HLA class II interaction may down-regulate low-affinity adhesion of resting T cells and, to some extent, high-affinity adhesion of T cells actively induced by CD3 cross-linking but not passively induced by an anti-CD 11a antibody 1 Introduction

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Section: Discussionsupporting

confidence: 90%

Regulation of LFA‐1‐mediated T cell adhesion by CD4

et al. 1991

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“…By binding to MHC class II molecules, CD4 serves as a coreceptor during Ag recognition by the TCR. This results in a marked increase in the sensitivity of a T cell to Ag presented by MHC class II, effectively lowering the dose of Ag required for activation by about 100-fold (2). To realize this function it has recently been proposed that CD4, by its ability to oligomerize, contributes to the formation of a cooperative assembly of TCR-MHC class II complexes (3)(4)(5).…”

mentioning

confidence: 99%

Glucocorticoids Regulate TCR-Induced Elevation of CD4: Functional Implications

Wiegers

Stec

Klinkert

et al. 2000

The Journal of Immunology

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CD4 serves as a coreceptor during Ag recognition by the TCR. This interaction results in a marked increase in the sensitivity of a T cell to Ag presented by MHC class II molecules. Here we report that activation of T cells either by plate-bound mAb (anti-TCR, anti-CD3) or soluble activators (staphylococcal enterotoxin A, Con A) is associated with an (up to 3-fold) increase in CD4 cell surface expression on CD25+ cells, which was maximal after 72–96 h. Incubation with the glucocorticoid hormone corticosterone (CORT) shifted the enhancement of CD4 expression to a point about 24 h earlier than that observed in control cultures. In parallel, the proliferative response of these CORT-treated cells was profoundly enhanced. An involvement of increased CD4 expression in this enhanced proliferative response was evidenced by the observation that T cell proliferation in CORT-treated cultures was much less sensitive to inhibition by an inhibitory, nondepleting anti-CD4 mAb than that in control cultures. TCR down-regulation was, however, not affected by CORT. Thus, based on this study and previous reports we propose that both TCR-mediated signals and glucocorticoids are important physiological regulators of CD4 expression. In addition, these findings may be of significance for the sensitivity of CD4+ cells to HIV infection upon T cell activation, as the efficacy of primary patient HIV entry depends on the level of surface CD4.

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“…For this reason CIITA-mediated MHC expression is central in the generation of an antigen-specific immune response by presenting antigenic peptides to the T-cell receptor (TCR) on T lymphocytes. 10,11 MHC class I molecules are expressed on almost all nucleated cells. In contrast, the constitutive expression of MHC class II molecules is restricted to specific immune cell types that include antigen-presenting cells such as dendritic cells, B lymphocytes, macrophages and thymic epithelial cells.…”

mentioning

confidence: 99%

Lack of ifn‐γ‐mediated induction of the class II transactivator (CIITA) through promoter methylation is predominantly found in developmental tumor cell lines

Stoep

Biesta

Quinten

et al. 2001

Intl Journal of Cancer

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The class II transactivator (CIITA) plays a pivotal role in the expression of major histocompatibility complex (MHC) class II and accessory genes (invariant chain [Ii] and HLA-DM), whereas it has an ancillary function in the expression of MHC class I and ␤ 2 -microglobulin (␤ 2 m) genes. 1-9 The MHC is a large multigene family that encodes cell surface glycoproteins involved in binding and presentation of antigenic peptides to T lymphocytes. The products of the ␤ 2 m, Ii and HLA-DM genes are also essential proteins in MHC class I-and class II-mediated antigen presentation function, respectively. For this reason CIITA-mediated MHC expression is central in the generation of an antigen-specific immune response by presenting antigenic peptides to the T-cell receptor (TCR) on T lymphocytes. 10,11 MHC class I molecules are expressed on almost all nucleated cells. In contrast, the constitutive expression of MHC class II molecules is restricted to specific immune cell types that include antigen-presenting cells such as dendritic cells, B lymphocytes, macrophages and thymic epithelial cells. Nonimmune cells lack constitutive expression of MHC class II; however, in most of these cells MHC class II expression can be induced by interferon-␥ (IFN-␥). 12,13 Notably, expression of MHC class I molecules can also be enhanced by IFN-␥. Together, the upregulated expression of MHC class I and class II molecules results in an increase in the immunogenic potential of cells. The importance of MHC expression by tumor cells in mounting an effective antitumor immune response has been shown in animal models for T-cell-mediated immunotherapy 14 -16 and is corroborated by the notion that tumors expressing high levels of both MHC class I and class II molecules display abundant lymphocytic infiltration. [17][18][19] Notably, patients with high tumorlytic lymphocyte infiltrates generally have a better prognosis. [17][18][19] Several tissues have been shown to exhibit a significantly reduced membrane expression of MHC class I molecules. In particular, certain reproductive and developmental tissues lack expression of MHC class I molecules, including sperm, 20 oocytes, 21 preimplantation embryos 22 and villous trophoblast cells. 23 The absence of MHC molecules from fetal and embryonic tissues creates an immune privilege for these cells during gestation and may be of functional significance during development. Also, several malignant cell types have been shown to lack the expression of MHC molecules. This reduced expression of MHC molecules will contribute to a decreased recognition by T cells, allowing an escape from immunosurveillance. 24 -26 Interestingly, most of the MHC-deficient tumor cells have originated from fetal or embryonic tissues. Downregulation of MHC gene expression in these embryonic or developmental tumors may therefore not result from the neoplastic transformation event but may instead reflect the characteristic silent state of MHC class I and class II genes during early development.To understand the mechanisms of downregulat...

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CD4+ T Cells: Specificity and Function

Cited by 260 publications

References 100 publications

Regulation of LFA‐1‐mediated T cell adhesion by CD4

Regulation of LFA‐1‐mediated T cell adhesion by CD4

Glucocorticoids Regulate TCR-Induced Elevation of CD4: Functional Implications

Lack of ifn‐γ‐mediated induction of the class II transactivator (CIITA) through promoter methylation is predominantly found in developmental tumor cell lines

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