Regulatory Clones Research Articles

Activated, but not resting human Th2 cells, in contrast to Th1 and T regulatory cells, produce soluble ST2 and express low levels of ST2L at the cell surface.

The T1/ST2 gene encodes, as a result of differential splicing, a cell surface protein (transmembrane form of T1/ST2, ST2L) and a soluble, secreted, protein (ST2). Here, we show that transcripts for both ST2L and ST2 are present in activated human Th2 clones, but not in Th1 and T regulatory clones. This activation-dependent expression of ST2L/ST2 transcripts was also found in short-term in vitro differentiated, activated CD4(+) Th2 cells. No expression of ST2L or ST2 mRNA was detected in any of the resting T cell subsets. Low cell surface expression of ST2L was detected on activated Th2 clones, and on freshly isolated non-IFN-gamma-producing CD4(+) peripheral blood T cells, activated with anti-CD3 and anti-CD28 mAb. Finally, ST2 could be detected in the culture supernatants of activated, but not resting, Th2 clones. Taken together, these results show that the T1/ST2 gene products are inducible proteins and that human Th2 cells, in addition to expressing ST2L at their cell surface, secrete ST2 following activation.

Regulatory Interactions among Autologous T Cell Clones Human Bifunctional T Cell Clones Regulate the Activity of an Autologous T Cell Clonea

In contrast to the ease of cloning and characterizing, at the molecular level, helper and cytotoxic T cells, suppressor T cells remain an enigma, and their existence as discrete entities is being increasingly challenged. Here we review evidence that CD4+ regulatory clones, capable of expressing both helper and suppressor functions, may account for much of the suppressor function. It is suggested that a single T cell clone, depending on the signals it receives from its environment, may release either helper or suppressor cytokines. Studying such clones under defined conditions (providing suppressor signals), may preclude detection of their helper capacity. Since some therapeutic approaches in various human diseases are based on the manipulation of helper and suppressor functions, the question whether committed suppressor cells exist has important practical implications in medicine.

Reciprocal expansions of idiotypic and anti-idiotypic clones following antigen stimulation

IT has been postulated by Jerne that a network of idiotypic and anti-idiotypic interactions between lymphocytes may constitute a principal form of immune regulation1,2. This network would control and ‘remember’ the antigen-induced activation of a particular (idiotypic) clone through its idiotopic or paratopic interactions with regulatory clones. These latter clones would in turn be regulated in the same fashion, creating what Jerne has called a ‘web of V-domains’ (ref. 2). Current experimental evidence strongly supports the concept of idiotype-directed regulation and also documents phenotypic complexity within the anti-idiotype response; for example, anti-idiotypic cells (and/or their products) may help or suppress the idiotypic response3–8. However, this apparent complexity does not diminish the importance of Jerne's basic premise that reciprocal activation between idiotypic and anti-idiotypic clones could establish an equilibrium system capable of regulating the immune response9–11. We present here evidence for oscillatory behaviour in the population dynamics of a single, antigen-stimulated clone and for the reciprocal behaviour of the specific anti-idiotypic (idiotype binding) clones.