Impaired germinal center responses and suppression of local IgG production during intracellular bacterial infection.
ABSTRACT Germinal centers (GCs) are specialized microenvironments in secondary lymphoid organs that facilitate the development of high-affinity, isotype-switched Abs, and immunological memory; consequently, many infections require GC-derived IgG for pathogen clearance. Although Ehrlichia muris infection elicits a robust expansion of splenic, IgM-secreting plasmablasts, we detected only very low frequencies of isotype-switched IgG-secreting cells in mouse spleens, until at least 3 wk postinfection. Instead, Ag-specific IgG was produced in lymph nodes, where it required CD4 T cell help. Consistent with these findings, organized GCs and phenotypically defined splenic GC B cells were found in lymph nodes, but not spleens. Ehrlichial infection also inhibited spleen IgG responses against a coadministered T cell-dependent Ag, hapten 4-hydroxy-3-nitrophenyl acetyl (NP)-conjugated chicken gamma globulin in alum. NP-specific B cells failed to undergo expansion and differentiation into GC B cells in the spleen, Ab titers were reduced, and splenic IgG production was inhibited nearly 10-fold when the Ag was administered during infection. Our data provide a mechanism whereby an intracellular bacterial infection can compromise local immunity to coinfecting pathogens or antigenic challenge.
Article: Spleen cell-mediated suppression of IgG production to a non-parasite antigen during chronic Trypanosoma cruzi infection in mice.[show abstract] [hide abstract]
ABSTRACT: Splenic plaque-forming cell (PFC) responses to TNP-BGG (thymus-dependent) and TNP-Ficoll (thymus-independent) were measured during acute and chronic T. cruzi infections produced in C57BL/10 mice. The number of anti-TNP PFC to both antigens was suppressed as has been shown. Approximately 40% of untreated mice survived acute disease to enter chronic T. cruzi infection characterized by a decrease in parasitemia, a reduction in spleen size, a return to normal of the IgM responses to TNP-BGG and TNP-Ficoll, persistant polyclonal activation, and continued suppression of the IgG responses to TNP-BGG. Mice that were drug-treated during the acute disease had high survival rates and similar immune response patterns, ie., suppressed IgG PFC responses to TNP-BGG and normal IgM PFC responses to TNP-BGG and TNP-Ficoll. The selective suppression of the IgG response was transferred to nonirradiated syngeneic recipients by Thy-1.2-positive cells present in the spleens of chronically infected mice. These observations may be interpreted to suggest the persistence of nonspecific suppressor T cells during chronic T. cruzi infections.The Journal of Immunology 11/1983; 131(4):1978-82. · 5.79 Impact Factor
Article: Possible involvement of nigrostriatal dopamine system in the inhibition of thyrotropin secretion in the rat.[show abstract] [hide abstract]
ABSTRACT: The dopaminergic inhibition of cold-stimulated thyrotropin (TSH) secretion was studied in male rats. Serum TSH levels were decreased by apomorphine (1 mg/kg i.p.) but not by dopamine (DA, 0.2--5 mg/kg s.c.). This effect of apomorphine was abolished by haloperidol (1 mg/kg i.p.), metoclopramide and sulpiride (10 mg/kg i.p.) but not by domperidone (0.1--5 mg/kg i.p.). Domperidone does not cross the blood-brain barrier while the other DA receptor antagonists do so. High doses of domperidone itself inhibited the cold-induced TSH secretion whereas the other DA antagonists did not. DA (1--10 micrograms/rat) into the medial basal hypothalamus (MBH) had no effect but 10--50 micrograms/rat into the 3rd ventricle inhibited the cold-stimulated TSH secretion. 6-Hydroxydopamine infusion after desipramine pretreatment (25 mg/kg i.p.) did not affect TSH secretion when given into the MBH (2 micrograms/rat), the 3rd ventricle (100 micrograms/rat) or unilaterally into the substantia nigra (SN, 6 micrograms/nucleus), but bilateral nigral infusions abolished the TSH cold response. The inhibitory effect of apomorphine (0.1 and 0.5 mg/kg i.p.) was amplified only in the rats whose SN was unilaterally destroyed. These results show that tuberoinfundibular DA neurons do not affect TSH secretion. Instead, the inhibition is mediated through the hypothalamic projections of the nigrostriatal DA system.European Journal of Pharmacology 01/1982; 76(4):403-9. · 2.52 Impact Factor