Vertebral osteomyelitis due to Lactobacillus paracasei in a diabetic patient. A case report and literature review.

Staphylococci are the most frequent cause of vertebral osteomyelitis, but infections due to unusual pathogens are also reported. We describe a rare case of spondylodiscitis due to Lactobacillus paracasei. A 74-year-old diabetic male was evaluated for fever and back pain. Blood cultures and vertebral biopsy were positive for Lactobacillus paracasei. He often took laxatives and probiotics for chronic constipation. After target treatment the patient improved but he died for a heart attack two months after the end of the treatment. Although Lactobacillus paracasei is usually not pathogenic, sepsis is described in immunocompromised patients while vertebral osteomyelitis is rare.

Nonantigen specific CD8+ T suppressor lymphocytes originate from CD8+CD28- T cells and inhibit both T-cell proliferation and CTL function.

Nonantigen specific CD8+ suppressor T lymphocytes (CD8+ Ts) inhibit T-cell proliferation of antigen-specific T lymphocytes. The impossibility to generate in vitro these cells has been correlated with the appearance of relapses in patients affected by autoimmune diseases, suggesting the involvement of these cells in immune regulation. This study was aimed to identify circulating precursors and to characterize the phenotype and mechanism of action of CD8+ Ts. We found that CD8+ Ts can be generated in vitro from CD8+CD28- T lymphocytes, but not from CD8+CD28+ T cells. A key role in their generation is played by monocytes that secrete interleukin-10 (IL-10) after granulocyte macrophage-colony-stimulating factor (GM-CSF) stimulation. Cell-to-cell direct interaction between CD8+CD28- T cells and monocytes does not play a role in the generation of CD8+ Ts. CD8+ Ts have a CD45RA+, CD27-, CCR7-, IL-10Ralpha+ phenotype and a TCR Vbeta chain repertoire overlapping that of autologous circulating CD8+ T cells. This phenotype is typical of T lymphocytes previously expanded due to antigen stimulation. Their suppressive effect on T-cell proliferation targets both antigen presenting cells, such as dendritic cells, and antigen-specific T lymphocytes, and is mediated by IL-10. CD8+ Ts suppress also the antigen-specific cytotoxic activity of CTL decreasing the expression of HLA class I molecules on target cells through IL-10 secretion. These findings can be helpful for the better understanding of immune regulatory circuits and for the definition of new pathogenic aspects in autoimmunity and tumor immunology.

Migration of V delta 1 and V delta 2 T cells in response to CXCR3 and CXCR4 ligands in healthy donors and HIV-1-infected patients: competition by HIV-1 Tat.

We show that HIV-1-infected patients have increased concentrations of circulating V delta 1 T cells (2.2%-9.0% of T lymphocytes; healthy donors, 1.0%-2%) and, in some instances, V delta 2 T cells (3.5%-4.8% vs 2.0%-3.3%). In these patients, both V delta 1 and V delta 2 T cells are CXCR3+CXCR4+, whereas in healthy donors CXCR4 was preferentially expressed on V delta 1 T lymphocytes. gamma delta T cells transmigrated across endothelial monolayers, in response to interferon-gamma-inducing protein-10 (IP-10/CXCL10), stromal cell-derived factor-1 (SDF-1/CXCL12), or both, according to the expression of the specific receptors CXCR3 and CXCR4. Interestingly, 6Ckine/SLC/CCL21 was more effective than IP-10/CXCL10 on V delta 1 CXCR3+ cells, whereas V delta 2 CXCR3+ cells were driven more efficiently by IP-10/CXCL10. IP-10/CXCL10- and SDF-1/CXCL12-induced transmigration was dependent on phosphoinositide-3 kinase (PI-3K), as demonstrated by the use of the specific blockers wortmannin and LY294002 and by the activation of the downstream serine kinase Akt/PKB on ligation of CXCR3 and CXCR4. Occupancy of CXCR3, but not of CXCR4, led to CAMKII activation; accordingly, the CAMKII inhibitors KN62 and KN93 decreased IP-10/CXCL10- but not SDF-1/CXCL12-driven transmigration. Finally, HIV-1 Tat, which is present in the serum of HIV-1-infected patients, interferes with the chemotactic activity of these chemokines because of the cysteine-rich domain of the protein, which contains CXC and CC chemokine-like sequences.