Intestinal helminth infection impacts the systemic distribution and function of the naive lymphocyte pool.

Homeostasis is a fundamental principle of biological systems. A paradigm of immune homeostasis is the remarkably constant number of naive T and B lymphocytes in the body that continuously circulate through the secondary lymphoid organs to maximize immune surveillance. Whether the dynamics and distribution of the systemic naive lymphocyte pool is affected following organ-specific infection is not known. Here we show that, following infection of mice with an enteric helminth, naive T and B lymphocytes accumulate in the T helper type 2-reactive mesenteric lymph node while they are concurrently depleted from non-draining peripheral lymph nodes. This systemic redistribution of naive lymphocytes is sustained into the chronic phase of the infection, requires lymphotoxin beta receptor-dependent signals and is associated with a reduced ability of parasitized animals to mount antigen-specific cellular and humoral immune responses to heterologous immunization or infection at peripheral sites. Our data suggest that the function of the homeostatic naive lymphocyte pool can be modulated by its systemic distribution following infection and may provide a novel concept underlying compromised immune responsiveness at peripheral sites in helminth-infected individuals.

Immune complexes present in the sera of autoimmune mice activate rheumatoid factor B cells.

The fate of an autoreactive B cell is determined in part by the nature of the interaction of the B cell receptor with its autoantigen. In the lpr model of systemic autoimmunity, as well as in certain human diseases, autoreactive B cells expressing rheumatoid factor (RF) binding activity are prominent. A murine B cell transgenic model in which the B cell receptor is a RF that recognizes IgG2a of the j allotype (IgG2aj), but not the b allotype, was used in this study to investigate how the form of the autoantigen influences its ability to activate B cells. We found that sera from autoimmune mice, but not from nonautoimmune mice, were able to induce the proliferation of these RF+ B cells but did not stimulate B cells from RF- littermate controls. The stimulatory factor in serum was found to be IgG2aj, but the IgG2aj was stimulatory only when in the form of immune complexes. Monomeric IgG2aj failed to stimulate. Immune complexes containing lupus-associated nuclear and cytoplasmic autoantigens were particularly potent B cell activators in this system. Appropriate manipulation of such autoantibody/autoantigen complexes may eventually provide a means for therapeutic intervention in patients with certain systemic autoimmune disorders.

5 alpha-reduced progesterone metabolites are essential in hamster VTA for sexual receptivity.

Progesterone's (P) actions in the ventral medial hypothalamus (VMH) and the ventral tegmental area (VTA) are essential for sexual receptivity in hamsters. This study investigates the notion that P works in the VTA in the absence of intracellular P receptors (PRs) by 5 alpha-reduction to progestins, which would subsequently bind to membrane gamma-Aminobutyric Acid receptor complexes (GBRs). To test the importance of P metabolism, a 5 alpha-reductase inhibitor, 17 beta-N, N-diethylcarbamoyl-4-methyl-4aza-5 alpha-androstan-3-one (4MA) was administered SC (0, 3, 9, 15, 24, or 30 mg/kg) to ovx estradiol benzoate(EB)-primed hamsters, followed by one of six doses of SC P (0, 25, 50, 100, 200, or 500 micrograms) and sexual receptivity testing. 200 micrograms P-treated animals administered higher (24 and 30 mg/kg) doses of 4MA had significantly decreased total lordosis durations (TLDs) compared to 0 mg/kg 4MA controls (exp 1). In exp 2, 4MA was aimed bilaterally at the VTA prior to SC P. After 200 micrograms P, animals had significantly lower TLDs than after 500 micrograms P, 3 hours following bilateral VTA implantation of 4MA, but not cholesterol. In exp 3, cycling female hamsters were infused with 1.0 microgram 4MA or vehicle unilaterally into the VTA on diestrus, proestrus, and estrus. 4MA, but not vehicle, infusions into the VTA interrupted receptivity in estrus and proestrus animals, but had no effect on diestrus animals. 4MA's reduction of receptivity when given systemically and intracranially strongly supports the hypothesis that 5 alpha-reduced P metabolites, possibly interacting with GBRs in the VTA, are essential for sexual receptivity in hamsters.