Differential Regulation of Human, Antigen-specific Th1 and Th2 Responses by the B-7 Homologues, CD80 and CD86

Abstract

A selectivity of B7.1 (CD80) for promoting Th1 responses and B7.2 (CD86) for promoting Th2 responses in the murine system has recently been suggested. The present study explores this hypothesis, using human PBMCs and antigen-specific Th1 and Th2 clones. Proliferative responses of peripheral blood mononuclear cells (PBMCs) from ragweed-allergic, tetanus toxoid-immunized individuals were downregulated by treatment with anti-CD86 in ragweed- and tetanus toxoid-driven cultures (% Inhibition = 55 +/- 4 and 61 +/- 12, respectively; P < 0.03 relative to untreated cultures). Gene expression in PBMCs for interleukin (IL)-4, IL-5, and interferon gamma (IFNgamma), assessed by reverse-transcriptase polymerase chain reaction, was also downregulated by treatment with anti-CD86 in both the ragweed- and tetanus toxoid-driven systems. Neither independent efficacy nor synergy with anti-CD86 was apparent with anti-CD80 treatment; two different anti-CD80 blocking antibodies yielded identical results. Conversely, antigen-specific Th1 and Th2 clones were insensitive to treatment with either anti-CD80, anti-CD86, or a combination of the two. Unaffected parameters included proliferative response (P < 0.14 and 0.33, respectively, for Th1 and Th2), proinflammatory cytokine gene expression, and cytokine protein secretion into culture supernatants (P < 0.44 and 0.16, respectively, for IL-4 and IFNgamma). We conclude that CD86 is the primary B7 signaling homologue in human PBMC responses, and that second signal pathways through the B7 homologues have no effect on phenotypically differentiated T helper cells in humans.

Balanced TH1 and TH2 immunopotentiating effects of silicates partly containing nanoparticles present in calcined serpentine

“…While the increase in TLR-2 expression on the cells from CS-treated hosts suggests immunopotentiation, it would be the secondary signals mediated by costimulatory molecules present on antigen-presenting cells that would ultimately prove important for promoting cell-cell crosstalk to activate T H cells for effective humoral or cell-mediated immune responses. In that context, CD86 is important in the enhanced proliferation of T H 2 cells (Hofer et al 1998;Jaffar et al 1999), whereas proliferation of T H 1 cells depends on induction of CD80 expression (Bashian et al 1997;Greenfield et al 1998). The results here showed that oral administration of CS enhanced the expression of both CD80 and CD86.…”

Immunomodulatory Effects of in vitroStress Hormones on FoxP3, Th1/Th2 Cytokine and Costimulatory Molecule mRNA Expression in Human Peripheral Blood Mononuclear Cells

“…CD28 binds with CD80 or CD86 as a further activation signal to upregulate specific cytokine production and/or effector function of T cells. It has been reported that CD28 binding with CD80 preferentially activates Th1 cells while CD28 binding with CD86 activates Th2 cells [38] . In contrast, CTLA4 typically downregulates the ongoing immune response and arises on the surface of the T cell relatively late in the process of cell activity.…”

Influence of Costimulatory Molecules on Immune Response toLeishmania majorby Human Cells In Vitro

“…The relatively small influence of CD80 in this system is an interesting finding in light of the marked up-regulation of CD80 on macrophages cultured with PBL and L. major. The mechanism(s) behind this lack of effect is unclear, but a low sensitivity to CD80 costimulation may be a characteristic of PBMC, as suggested by others (2,23).…”