Atterns of Lymphokine Production by Primary Antigen-Specific/MHC Restricted Murine Helper T Cell Clones

Abstract

In this study we examined a panel of CD4+ antigen specific/MHC restricted T cell clones for their ability to secrete IL-2, IL-4, and IFN-gamma upon stimulation with con A, three lymphokines which are diagnostic for the TH1 and TH2 subtypes of helper T cells. Eight of the twelve clones we analyzed did not fit the classical TH1/TH2 patterns of lymphokine secretion. Seven of these clones secreted both IL-2 and IL-4 and two of these also produced IFN-gamma. The remaining non-classical clone secreted IL-4 and IFN-gamma but not IL-2. Data from the subcloning of the IL-2/IL-4/IFN-gamma triple producers were not consistent with the parental lines being a mixture of TH1 and TH2 cells. The IL-2/IL-4 double producers (IFN-gamma negative) cannot be explained by the parental lines being a mixture of the TH1 and TH2 subtypes. Nevertheless, these double producers were subcloned and the results provided convincing evidence that clones which secrete both IL-2 and IL-4 do exist. Lymphokine loss variants involving IL-2, IL-4 or IFN-gamma were observed among subclones derived from the double and triple producers as well as in several parental lines maintained in continuous culture. We also observed the appearance of inducible IFN-gamma production in some subclones derived from parental clones where production of IFN-gamma was not detectable. The phenotypes of these variants failed to indicate an obvious trend toward the TH1 and TH2 subtypes. Thus, our results suggest that more heterogeneity in the population of CD4+ helper T cells exists than can be explained by the TH1 and TH2 subtypes of these cells.

The profiles of interleukin (IL)‐2, IL‐6, and interferon‐gamma production by peripheral blood mononuclear cells from house‐dust‐mite‐allergic patients: a role for IL‐6 in allergic disease

“…This confirms our previous preliminary findings of IFN-y secretion from stimulated PBMC (18) and is consistent with data from allergen-specific T-cell clones which appear to secrete little or no IFN-y (30). However, studies with TCC suggest that impaired IFN-y production occurs only in allergen-specific TCC in atopic subjects, whereas antigen-specific TCC from atopic subjects produce high levels of IFN-y (7). Our data suggest a broader defect in the IFN-y response in atopic subjects, because this was impaired in response to both allergen and antigen stimulation.…”

“…This may be important because it is becoming clear that the distinction between THI and TH2 cells is not absolute: both cell types may exist in an individual in response to the same stimulus (21), and clones have been described which secrete both T^l and TH2 cytokines (20). Such clones have been classified as T^O cells and may represent either a precursor subset of TH cells or a phenotypically stable intermediate subset (7,20,30).…”

“…Additionally, it is now widely recognized that an intermediate or precursor subset also exists, the T^O phenotype. These cells can secrete an overlapping combination of cytokines which individually contribute to the discrete T,, 1 and Ty^l extremes (7). A predominantly T,,2 response leads to IgE production and activation of mast cells and eosinophils, whereas a T^l response inhibits IgE production.…”

Peripheral blood mononuclear cells from house dust mite allergic patients produce IL‐2 in response to specific allergen challenge

“…However, IL-2 production has traditionally been associated with THI cells: in the mouse IL-2 secretion is restricted to TH i cells [3] and in man the response to non-allergenic antigens is typically THI in type, with high levels of IL-2 production [11]. Further, certain murine and human T cell clones, which simultaneously secrete Tnl and TH2 cytokines, have been established [27,28], demonstrating that there can be heterogeneity in this system.…”