Immune factors and immunoregulation in tuberculosis.

Pathogens causing tuberculosis and other chronic infectious diseases of major public health importance commonly have complex mechanisms involved in their persistence in the host despite specific and sometimes strong immune responses. These diseases are also associated with the lack of efficient vaccines, difficult therapeutics and a high mortality rate among susceptible individuals. Here, we will review features of the host immune response that contribute to the occurrence of disease. In addition, we propose that the immune responses observed in tuberculosis cannot be interpreted solely on the basis of a Th1-Th2 counter-regulatory paradigm since there is growing evidence that natural regulatory T cells may play an important role in the regulation of host immune responses against Mycobacterium tuberculosis. Thus, the development of more effective vaccines against this bacterial disease should take into account the role of natural regulatory T cells in the progression to severe disease and persistence of infection. Finally, new treatments based on manipulation of regulatory T cells should be investigated.

Immune factors and immunoregulation in tuberculosis

Pathogens causing tuberculosis and other chronic infectious diseases of major public health importance commonly have complex mechanisms involved in their persistence in the host despite specific and sometimes strong immune responses. These diseases are also associated with the lack of efficient vaccines, difficult therapeutics and a high mortality rate among susceptible individuals. Here, we will review features of the host immune response that contribute to the occurrence of disease. In addition, we propose that the immune responses observed in tuberculosis cannot be interpreted solely on the basis of a Th1-Th2 counter-regulatory paradigm since there is growing evidence that natural regulatory T cells may play an important role in the regulation of host immune responses against Mycobacterium tuberculosis. Thus, the development of more effective vaccines against this bacterial disease should take into account the role of natural regulatory T cells in the progression to severe disease and persistence of infection. Finally, new treatments based on manipulation of regulatory T cells should be investigated.

Intraembryonic, but not yolk sac hematopoietic precursors, isolated before circulation, provide long-term multilineage reconstitution.

The relative contribution of yolk sac and intraembryonic precursors to hematopoiesis has been a matter of long-standing controversy. As reconstitution activity has so far only been found in embryonic tissues after the onset of circulation, the origin of reconstituting cells could not be formally established. Here, we separated yolk sac and intraembryonic splanchnopleura prior to circulation and maintained the explants in organ culture before transfer. Precursors derived from the intraembryonic site generated multilineage hematopoietic progeny in adult mice for more than 6 months. Yolk sac cells only provided myeloid short-term reconstitution. The results reveal a differential hematopoietic capacity of precirculation embryonic tissues in vivo, and indicate that the only cells capable of adult long-term hematopoiesis are of intraembryonic origin.

Characterization of T cell precursor activity in the murine fetal thymus: evidence for an input of T cell precursors between days 12 and 14 of gestation.

In the mouse, the number and the differentiation potential of thymic migrants remain controversial. A fetal thymic organ culture under limiting dilution conditions allowed us to show a 130-fold increase in the numbers of T cell precursors in the embryonic thymus between days 12 and 14 of gestation. A comparative analysis of the most immature thymocytes at these two stages revealed that: (1) CD44(+)CD25(-) (DN1) thymocytes at 14 days post coitum (dpc) efficiently differentiate into mature T cells both in vivo and in vitro; (2) 12dpc thymocytes exhibit a low frequency of T cell precursors and were unable to generate a detectable progeny after in vivo intrathymic transfer. A 48-h organ culture of 12dpc thymic lobes did neither correct the low frequency of T cell precursors nor the absence of expression of T cell-specific genes observed in 12dpc thymocytes. We thus concluded that a fraction of recent thymic immigrants contribute to the observed properties in DN1 14dpc thymocytes. We show that increasing numbers of T cell precursors migrate to the thymus from 11 to 14 dpc. We propose that the first thymic immigrants do not contribute significantly to T cell generation which depends on the subsequent colonization by cells with a high T cell precursor potential.

Intercomparison of calibration procedures for 192Ir HDR sources in Brazil.

The lack of well established dosimetry protocols for HDR sources is a point of great concern regarding the uniformity of procedures within a particular country and worldwide. The main objective of this paper is to report the results from ten institutions of an intercomparison of calibration procedures for 192Ir HDR sources currently in use in Brazil. The treatment irradiator of one institution was calibrated by a reference system and used by all participants with their own measuring electrometers and ionization chambers under the same experimental conditions. Two methods were used: the calibration jig and the well-type ionization chamber. Each participant was allowed to use their own method and formalism. The results of this exercise were very positive since this was the first time in Brazil that a group of users gathered to share their experience and openly discuss the physical concepts behind the calibration procedures. The results were all within +/-3.0%, except one case where -4.6% was observed and later identified as a problem with the Nk value for x-rays. Though the magnitude of the deviations found was generally acceptable considering the diversity of formalisms currently in use, a proposal is now being prepared to be adopted as a national protocol. The identification of the institutions was left out for the sake of confidentiality.