SummaryThe effects exerted on the in vitro development of antigen-specific T cell lines and T cell clones by addition or neutralization of interleukin 12 (I1:12) in lymphocyte bulk culture were examined. T cell lines specific for Dermatophagoides pteronyssinus group I (Der p I) derived in the presence of I1:12 exhibited reduced ability to produce I1:4 and increased ability to produce interferon "/(IFN-3~), and developed into Der p I-specific CD4 § T cell clones showing a T helper type 0 (Th0)-or Thl-, instead of Th2-, like cytokine profile. In contrast, purified protein derivative (PPD)-specific T cell lines derived in the presence of anti-I1:12 antibody exhibited an increased ability to produce I1:4 and developed into PPD-specific CD4 + T cell clones showing a Th0-, instead of Thl-, like profile. The influence of IL-12 on the cytokine secretion profile of Der p I-specific T cell lines was not prevented by addition to lymphocyte bulk cultures of anti-IFN-y antibody, but could be at least partially inhibited by the removal from bulk cultures of CD16 + cells. Thus, IL-12 and CD16 + cells appear to have inhibitory effects on the development of IL-4-producing cells and to play an inductive role in promoting Thl-like responses.

SummaryInterleukin 12 facilitates the generation of a T helper type 1 (Thl) response, with high interferon 3' (IFN-3') production, while inhibiting the generation of IL-4-producing Th2 calls in polyclonal cultures of both human and murine T cells and in vivo in the mouse. In this study, we analyzed the effect of IL-12, present during cloning of human T cells, on the cytokine profile of the clones. The culture system used allows growth of clones from virtually every T cell, and thus excludes the possibility that selection of precommitted Th cell precursors plays a role in determining characteristics of the clones. IL-12 present during the cloning procedures endowed both CD4 + and CD8 + clones with the ability to produce IFN-3" at levels severalfold higher than those observed in clones generated in the absence of IL-12. This priming was stable because the high levels of IFN-3' production were maintained when the clones were cultured in the absence of IL-12 for 11 d. The CD4 + and some of the CD8 + clones produced variable amounts of IL-4. Unlike IFN-3', IL-4 production was not significantly different in clones generated in the presence or absence of IL-12. These data suggest that IL-12 primes the done progenitors, inducing their differentiation to high IFN-3'-producing clones. The suppression of IL-4-producing cells observed in polyclonally generated T cells in vivo and in vitro in the presence of IL-12 is not observed in this donal model, suggesting that the suppression depends more on positive selection of non-IL-4-producing cells than on differentiation of individual clones. However, antigen-specific established Th2 clones that were unable to produce IFN-3, with any other inducer did produce IFN-3" at low but significant levels when stimulated with IL-12 in combination with specific antigen or insoluble anti-CD3 antibodies. This induction of IFN-3' gene expression was transient, because culture of the established clones with IL-12 for up to 1 wk did not convert them into IFN-3" producers when stimulated in the absence of IL-12. These results suggest that Th clones respond to IL-12 treatment either with a stable priming for IFN-3' production or with only a transient low level expression of the IFN-3" gene, depending on their stage of differentiation. ecent work from our and other laboratories (1-5) has shown that human CD4 + Th cell clones, in analogy to the murine system (6, 7), can be subdivided into at least three distinct functional subsets based on their cytokine secretion profile. One type of CD4 § done (Thl) produces IL-2, IFN-3`, and TNF-j3, but not IL-4 or IL-5; a second type (Th2) produces IL-4 and IL-5, but not IL-2, IFN-3`, or TNF-B; R. Manetti and F. Gerosa contributed equally to this work. and a third type (Th0) produces both Thl-and Th2-type cytokines (1,3,5,6). Although most CD8 + human T cell dones exhibit a Thl-like cytokine profile (3, 5), some CD8 + clones showing a Th2-1ike phenotype have also been described (s, 9).Several factors can affect the development of Thl or Th2 responses both in v...

SummaryWe analyzed at clonal level the functional profile of circulating or skin-infiltrating T lymphocytes from two individuals infected with the human immunodeficiency virus type 1 (HIV-1), suffering from a Job's-like syndrome (eczematous dermatitis, recurrent skin and sinopulmonary infections, and hypergammaglobulinemia E) and showing virtually no circulating CD4 + T cells. Most of the CD3 + T cell clones generated from both patients were CD4-CD8 + TCRc~/3 + . The others were CD4-CD8-TCRc~B + which exhibited reduced mRNA expression for the CD8 molecule or no mRNA expression for either CD4 or CD8 molecules. The great majority of both CD4-CD8 + and CD4-CD8-did not produce interferon (IFN) 3/and exhibited reduced cytolytic activity. Rather, most of them produced large amounts of both interleukin (IL) 4 and IL-5 and provided B cell helper function for IgE synthesis. These data suggest that a switch of cytolytic CD8 + T cells showing a Thl-like cytokine secretion profile to cells that make Th2-type cytokines, exhibit reduced cytolytic potential, and provide B cell helper function can occur in the course of HIV-1 infection. These cells may contribute to the reduced defense against viral infections and intracellular parasites and account for the elevated IgE serum levels, eosinophilia, and the allergic-like clinical manifestations seen in a proportion of HIV-l-infected individuals.

Our data suggest that Th17, Th0, and Th2 cells, respectively, may have a role in the pathogenesis of erosive and reticular oral lichen planus.

SummaryA large panel of CD8 + T cell clones generated from peripheral blood lymphocytes (PBL) of healthy donors or human immunodeficiency virus (HIV)-infected individuals were assessed for both cytokine secretion profile and CD30 expression and release. The great majority of CD8 + T cell dones generated from healthy individuals showed the ability to produce interferon 3' (IFN-3'), but not interleukin 4 (IL-4), and none of them either expressed membrane CD30 or released substantial amounts of soluble CD30 (sCD30) in their supernatant. In contrast, high numbers of CD8 + T cell clones generated from HIV-infected individuals, which produced IL-4 (and IL-5) in addition to IFN-3' or IL-4 (and IL-5) alone, expressed membrane CD30 and released detectable amounts of sCD30 in their supernatants. Indeed, CD30 expression appeared to be positively correlated with the ability of CD8 + T cell clones to produce IL-4 and IL-5 and inversely correlated with their ability to produce IFN-% whereas no correlation between CD30 expression and production of IL-10 was observed. These data suggest that CD30 is a marker for CD8 + T cells that have switched to the production of type 2 helper cytokines.