Interleukin 7 is a crucial factor for the development of murine T and B lymphocytes. We now report that, in the absence of interleukin 7, B lymphocyte production takes place exclusively during fetal and perinatal life, ceasing after 7 wk of age. In peripheral organs, however, the pool of B lymphocytes is stable throughout adult life and consists only of cells that belong to the B1 and marginal zone (MZ) compartments. This is accompanied by a 50-fold increase in the frequency of immunoglobulin (Ig)M- and IgG-secreting cells, and the concentration of serum immunoglobulins is increased three- to fivefold. Both the MZ phenotype and the increase in serum IgM are T cell independent. These findings reveal a previously undescribed pathway of B lymphopoiesis that is active in early life and is interleukin 7 independent. This pathway generates B1 cells and a normal sized MZ B lymphocyte compartment.

The CD4+ T cell‐mediated inflammatory response to Pneumocystis carinii (PC) critically contributes to the clinical severity of PC pneumonia. It has been suggested that lymphopenic conditions predispose individuals to this immunopathology, although the mechanisms remain poorly understood. Another set of evidence indicates that a subpopulation of CD4+ T cells constitutively expressing the CD25 molecule prevent lymphopenia‐induced autoimmunity and inflammatory bowel disease. We tested the ability of this CD25+CD4+ population to regulate CD4+ T cell‐mediated inflammatory response to PC. Adoptive transfer of CD25–CD4+ cells into PC‐infected recombination‐activating gene‐2‐deficient mice led to lethal pneumonia within 13 days post‐transfer. PC infection appeared to trigger CD25–CD4+ cells, since recipients with reduced PC load survived up to 5 weeks after transfer. In contrast, transferof CD25+CD4+ cells did not induce lethal pneumonia and prevented the development of the disease induced by CD25–CD4+ cells. Furthermore, CD25–CD4+ cells reduced the PC load in the lung, while CD25+CD4+ cells suppressed this immune response. Our results indicate an essential role for CD25+CD4+ T cells in the control of PC‐driven immunopathology, and suggest that in immunocompromised hosts PC pneumonia may result from a deficiency in regulatory T cells.

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Little progress has been achieved over the last 20 years on the clinical management of several conditions that relate to self-tolerance and to the regulation of immune responses: autoimmune diseases, transplantation tolerance, tumor immunity, allergy and vaccine development in chronic infections. These failures, it is argued, are due to the inability of the prevalent "recessive tolerance" concepts to accommodate physiological autoreactivity and the regulatory potential it embodies. In this review, the advantages of "dominant tolerance" models are underlined in the light of critical evidence and in the general context of the natural autoimmune activities. The role of regulatory T cells is discussed, notably in the regulation of inflammatory reactions and, more generally, in the "quality control" of immune responses. It is anticipated that progress will be brought about by dominant tolerance approaches, and through an increased knowledge of the differentiative pathways, repertoires, mechanisms of activation and effector functions of autoreactive, regulatory T cells.

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