"Suppressor Factor" of Neutrophils: A Short Story of a Long-Term Misconception.

A large body of evidence obtained during the last decade has demonstrated that neutrophils suppress T cell proliferation in different models of inflammation and cell interaction. The commonly used method for assessing cell proliferation and proliferation inhibition is measuring [3H]thymidine incorporation into cells. Earlier, we observed inhibition of [3H]thymidine uptake in experiments on neutrophil-mediated regulation of T cell response in tuberculosis immunity. Here, we used different types of proliferating cells to analyze the nature of the soluble "neutrophil factor" by a variety of methods (dialysis, HPLC, mass spectrometry, and NMR) and unambiguously demonstrated that neutrophils do not synthesize a specific factor inhibiting cell proliferation, but secrete high concentrations of extracellular thymidine that competitively inhibit [3H]thymidine incorporation. Although the physiological significance of thymidine secretion by neutrophils remains unknown, this phenomenon should be carefully considered when designing test systems for studying cell-cell interactions.

Formation of compact aggregates of B-lymphocytes in lung tissue during mycobacterial infection in mice depends on TNF production by these cells and is not an element of the host's immunological protection.

Tumor necrosis factor (TNF) plays a pivotal role in the early control of Mycobacterium tuberculosis and M. avium infections by a host. It was previously shown that both phagocyte-derived and T-cell-derived TNF productions are critical for protective immunity against M. tuberculosis, but the role of TNF produced by B-cells remained unclear. By comparing mice with B-cell-specific TNF deletion to littermate control mice, here we show that TNF production by B-lymphocytes is essential for the formation of infection-specific aggregates of B-cells in the lung. It is likely that these compact foci represent a pathogenic feature of inflammatory response rather than an element of protective immunity, since the capacity to form aggregates has no influence on the severity of M. tuberculosis- and M. avium-triggered diseases.

[Study of a role of B cells in the formation of antituberculosis immunity].

The authors have earlier demonstrated that CBA/N mice bearing nonsense mutation in the btk gene encoding B cell Bruton's thyrosine kinase after CG vaccination develop no protective response against subsequent M. tuberculosis H37Rv challenge. Adoptive transfer approaches are applied to show that this defect is determined by lymphoid cells and B lymphocytes play an essential role in its expression. In addition, experiments on CBA/N-xid mice with crude mixtures of soluble mycobacterial antigens suggest that the processing of live BCG could be impaired in the antigen-presenting cells of these mice.