T-cells In Pathogenesis Research Articles

Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods

BackgroundAn estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial.ResultsHere, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets.ConclusionsThus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

Aggravation of murine experimental allergic encephalomyelitis by administration of T-cell receptor γδ-specific antibody

Experimental allergic encephalomyelitis (EAE) is thought to be dominantly mediated by Ag-specific CD4 + MHC class II-restricted T-cells. Recent reports demonstrated accumulation of γ δ T-cells in active multiple sclerosis (MS) plaque and infiltration into brains with EAE. However, the role of γ δ T-cells in pathogenesis of EAE remains unknown. In the present study we have examined EAE mice administered T-cell receptor (TCR) γ δ-specific mAb (UC7-13D5) to elucidate the potential role of γ δ T-cells in the pathogenesis of EAE. MAb treatment led to transient depleting γ δ T-cells in vivo. MAb-treated EAE mice showed aggravation and disease recurrence and also increased Ag-specific proliferative responses. Semiquantitative PCR analysis demonstrated an increased level of IFN- γ mRNA expression in splenocytes from mAb-treated EAE mice during the induction and pre-relapse phase, however, aggravation and disease recurrence have not been suggested to be directly mediated by IFN- γ in the present study. Our results imply that γ δ T-cells play a preventing role in the recurrence of EAE.

Role of neutralizing antibodies and T-cells in pathogenesis of herpes simplex virus infection in congenitally athymic mice

Congenitally athymic nude mice were infected with 10 4 p.f.u. herpes simplex type I (strain SC16). Following the passive transfer of neutralizing monoclonal antibodies (AP 7, AP 8 and AP 12) it was observed that AP 7 alone reduced the virus infectivity in the nervous system; AP 8 and AP 12 failed to protect mice probably due to poor in vivo binding to the neutralization site on the virus. Latent ganglionic infection could be established in nude mice following adoptive transfer of optimum number (2 × 10 7 cells/mouse) of immune lymph node cells from day 7 herpes virus-infected hairy immunocompetent donor mice. Moreover, in some of the immune lymph node cell protected nudes, latency could be maintained even in complete absence of neutralizing antibodies. Results of ear-ablation experiments revealed that removal of primary source of infection after day 5 of infection reduced the amount of virus in the ganglia and spinal cord. Acute neurological infection was not detected following transfer of protective anti-gp-D neutralizing antibody (LP 2) in combination with removal of infected pinna. These data suggest that continuous seeding of virus occurs in related ganglia via the axonal route from infected ear pinna. It appears that local T-cell-mediated immune mechanisms are involved in maintenance of latency.