Martha W. Bond

Diversity of cytokine synthesis and function of mouse CD4+ T cells

The immune response is capable of invoking a variety of difTerent effector mechanisms, each of which is particularly effective against a certain set of pathogens. The regulation of the type of effector mechanisms chosen during an immune response is of critical importance to the host, and thus it is not surprising that this aspect of the immune system is subject to precise and complex regulation. Over the past few years, it has become clear that subsets of T cells secreting distinct patterns of cytokines have a major role in the regulation of the effector functions induced against a particular infectious agent. Two major patterns of cytokine synthesis were initially recognized, and these two patterns appear to correlate with the induction of delayed-type hypersensitivity (DTH) and help for antibody synthesis, thus providing a possible explanation for the separate and often reciprocal regulation of these two responses. Recent information suggests that additional cytokine secretion phenotypes exist, and that there is extensive regulation of the differentiation and effector function of the various cell types.

Identification of a novel thymocyte growth-promoting factor derived from B cell lymphomas

We found a unique thymocyte growth-promoting activity in supernatants (SN) from subclones of the B cell lymphoma CH12.LX. We have tentatively named this activity B-TCGF (for B cell-derived T cell growth factor) and characterized the activity produced by the CH12.LX.4866 subclone. This SN did not induce thymocyte proliferation alone, however, it enhanced both adult and fetal (Day 15 of gestation) murine thymocyte proliferation in the presence of IL-2, IL-4, or IL-7. Other known cytokines were screened for a B-TCGF-like activity using both adult and fetal thymocytes. IL-6 was found to be active only on adult thymocytes, while TNF alpha and GM-CSF were found to be active only on fetal thymocytes. However, neutralizing antibodies against these cytokines did not block the B-TCGF activity present in CH12.LX.4866 using either adult or fetal thymocytes. These observations suggest that the B-TCGF activity is mediated by a novel factor(s). The apparent molecular weight of this novel molecule(s) was 27-50 kDa determined by sizing HPLC.

Heterogeneity of Mouse Helper T Cells and Cross-Regulation of TH1 and TH2 Clones

The immune response against most antigens or infections shows a characteristic pattern of effector functions, typical of that antigen. For many pathogens, the immune response is appropriate, i.e. the effector functions are capable of neutralising or eliminating the infection. Examples include the induction of antibodies to neutralize toxins, cytotoxic T lymphocytes (CTLs) to kill virus-infected cells, and Delayed Type Hypersensitivity against intracellular pathogens. The mechanisms controlling this immune class regulation have been difficult to determine until recently, when two functionally different types of T cell were defined according to their different patterns of cytokine synthesis. These two T cell types appear to be responsible for at least part of immune class regulation.