Interleukin-12 primes human CD4 and CD8 T cell clones for high production of both interferon-gamma and interleukin-10.

Abstract

SUmlTlaryInterleukin-12 (IL-12) induces differentiation of T helper 1 (Thl) cells, primarily through its ability to prime T cells for high interferon-~/ (IFN-~) production. We now report that the presence of IL-12 during the first several days of in vitro clonal expansion in bruiting dilution cultures of polyclonally stimulated human peripheral blood CD4 + and CD8 + T cells also induces stable priming for high IL-10 production. This effect was demonstrated with T cells from both healthy donors and HIV(+) patients. Priming for IL-4 production, which requires IL-4, was maximum in cultures containing both IL-12 and IL-4. IL-4 modestly inhibited the IL-12-induced priming for IFN-% but almost completely suppressed the priming for IL-10 production. A proportion of the clones generated from memory CD45RO + cells, but not those generated from naive CD451KO-CD4 + T cells, produced some combinations of IFN-% IL-10, and IL-4 even in the absence of IL-12 and IL-4, suggesting in vivo cytokine priming; virtually all CD4 § clones generated from either CD45RO(-) or (+) cells, however, produced high levels of both IFN-~/and IL-10 when IL-12 was present during expansion. These results indicate that each Thl-type (IFN-~/) and Th2-type (IL-4 and IL-10) cytokine gene is independently regulated in human T cells and that the dichotomy between T cells with the cytokine production pattern of Thl and Th2 cells is not due to a direct differentiation-inducing effect of immunoregulatory cytokines, but rather to secondary selective mechanisms. Particular combinations ofcytokines induce a predominant generation ofT cell clones with anomalous patterns of cytokine production (e.g., IFN-~ and IL-4 or IFN-~/ and IL-10) that can also be found in a proportion of fresh peripheral blood T cells with "memory" phenotype or clones generated from them and that may identify novel Th subsets with iminunoregulatory functions.

Contrary Roles of IL‐4 and IL‐12 on IL‐10 Production and Proliferation of Human Tumour Reactive T Cells

“…Conversely, the addition of IFN-g, anti-IL-4 or IL-12 to in-vitro cultures of in-vivo primed T cells shifted the cytokine pattern of memory T cells to a Th1-like profile in murine [15,18] as well as in human T cell immune responses [17,19]. These results correspond to the results of two studies published while this manuscript was in preparation [21,22]. Meyaard and coworkers showed that IL-12 induced IL-10 production in freshly isolated human T cells as well as in T cell clones.…”

“…Gerosa and coworkers showed that polyclonally stimulated CD4 + and CD8 + T cell clones, which were established in the presence of IL-12, produced high levels of IL-10 and IFN-g. In contrast, IL-4 suppressed the development of IL-10 producing T cell clones [22]. Corresponding to these in vitro results, IL-12 injection into mice induced the production of IL-10 and IFN-g in vivo [23].…”

Neonatal Administration of IL-12 Enhances the Protective Efficacy of Antiviral Vaccines

“…We also examined the expression of IL-10, which is known to be induced in both neonates and adult mice by IL-12 treatment (23,28,29). Analysis of neonatal splenic mRNA revealed an absence of IL-10 mRNA expression in animals that received vaccine alone or PBS-NMS alone.…”

ChlamydiapneumoniaeInhibits Apoptosis in Human Peripheral Blood Mononuclear Cells Through Induction of IL-10

“…RIAs for human IL-12 p40, IL-12 p70, TNF-␣, and IL-10 were performed as previously described (21)(22)(23)(24), using mAb pairs C11.79/C8.6, 12H4/C8.6, B154.9/B154.7, and 9D7/12G8, respectively.…”