Contribution Of Cellular Immunity Research Articles

T Cell Response in Acute Motor Axonal Neuropathy

There is evidence that in the acute axonal motor neuropathy (AMAN) subtype of Guillain-Barré syndrome antibodies to gangliosides, produced through molecular mimicry by antecedent Campylobacter jejuni (C. jejuni) infection, attack gangliosides expressed in human peripheral nerve axolemma, inducing a primary axonal damage. The aim of this study is to investigate whether the T cell response has a role in AMAN pathogenesis. We isolated monocytes from 4 healthy subjects and 5 AMAN patients with antecedent C. jejuni infection and antibodies to GM1 and/or GD1a gangliosides. Immature dendritic cells expressing CD1 molecules cultured with autologous T cells were stimulated with 2 lipopolysaccharides (LPSs) extracted from C. jejuni strains containing GM1 and GD1a-like structures and with GM1 and GD1a. The T cell response to LPSs and to gangliosides was determined by measuring the release of IFN-gamma and TNF-alpha. We observed a T cell response to both LPSs in controls and AMAN patients, whereas only AMAN patients showed T cell reactivity to gangliosides GM1 and GD1a with a tight correlation between T cell reactivity to the ganglioside and individual antibody responses to the same ganglioside. T cells responding to gangliosides were CD1c-restricted CD8 positive and CD27 negative. These findings indicate a contribution of cellular immunity in the pathogenesis of AMAN. A possible role for ganglioside-reactive T cells might be to facilitate the production of antibodies against gangliosides.

Leukotriene B 4 is essential for selective eosinophil recruitment following allergen challenge of CD4 + cells in a model of chronic eosinophilic inflammation

Subcutaneous heat-coagulated egg white implants (EWI) induce chronic, intense local eosinophilia in mice, followed by asthma-like responses to airway ovalbumin challenge. Our goal was to define the mechanisms of selective eosinophil accumulation in the EWI model. EWI carriers were challenged i.p. with ovalbumin and the contributions of cellular immunity and inflammatory mediators to the resulting leukocyte accumulation were defined through cell transfer and pharmacological inhibition protocols. Eosinophil recruitment required Major Histocompatibility Complex Class II expression, and was abolished by the leukotriene B4 (LTB4) receptor antagonist CP 105.696, the 5-lipoxygenase inhibitor BWA4C and the 5-lipoxygenase activating protein inhibitor MK886. Eosinophil recruitment in EWI carriers followed transfer of: a) CD4 + (but not CD4 −) cells, harvested from EWI donors and restimulated ex vivo; b) their cell-free supernatants, containing LTB4. Restimulation in the presence of MK886 was ineffective. CC chemokine receptor ligand (CCL)5 and CCL2 were induced by ovalbumin challenge in vivo. mRNA for CCL17 and CCL11 was induced in ovalbumin-restimulated CD4 + cells ex vivo. MK886 blocked induction of CCL17. Pretreatment of EWI carriers with MK886 eliminated the effectiveness of exogenously administered CCL11, CCL2 and CCL5. In conclusion, chemokine-producing, ovalbumin-restimulated CD4 + cells initiate eosinophil recruitment which is strictly dependent on LTB4 production.

T cells in glomerulonephritis.

The involvement of immunoglobulin and complement in glomerulonephritis has been recognized for many decades, but the involvement of sensitized T cells and the contributions of cellular immunity have only recently been appreciated. The relative contributions of humoral and cellular immunity in the immunopathogenesis may be an important determinant of the various histological patterns and clinical features of human glomerulonephritis. Subsets of T helper cells, Th1 and Th2, induce immune activation with distinct patterns of involvement of immunoglobulin isotypes and cellular immune effectors. The relative activation of Th subsets is determined by a variety of factors including the nature, dose and mode of presentation of antigens and the cytokine milieu. The balance of Thl/Th2 activation may be important in directing effector pathways and patterns of injury in glomerulonephritis. In the effector phase, T cells are most prominent in proliferative and crescentic glomerulonephritis, where they are usually associated with other mediators of delayed-type hypersensitivity including macrophages and fibrin. In anti-neutrophil cytoplasmic antibody-associated crescentic glomerulonephritis, T cells are invariable participants, frequently in the absence of glomerular antibody deposition. In these forms of glomerulonephritis, which characteristically have a rapid course and poor outcome, T cells are likely to play a pivotal effector role.

The influence of neonatal thymectomy on the development of radiation myelopathy in rats

To investigate the possible contribution of cellular immunity in the development of radiation injury of the central nervous system, Wag/Rij rats were thymectomized at birth and irradiated to the cervical spinal cord at the age of 3 months. At the lime of paralysis or at the end of the follow-up period (when rats were 1-year-old) the animals were sacrificed and the mediastinum was examined histologically. In 95% of the neonatally thymectomized animals no thymus was left. These rats showed a firm impairment of the cellular immunity, as they had a 40% reduction of the T-lymphocytes in the spleen, and a 70% reduction of the mixed lymphocyte reaction, compared to age-matched controls. Both single dose and two-fraction irradiation experiments were performed. No modification of the latency time to develop paralysis was observed comparing thymectomized and age-matched controls. The incidence of foreleg; paralysis after cervical spine irradiation (single dose or two-fraction) was identically distributed in the follow-up period for both neonatally thymectomized and control Wag/Rij rats. The ED 50 value derived in the single dose experiments was 20.3 Gy for the control animals, and 20.9 Gy for thymectomized rats, and in the two fraction experiments 29 Gy for controls and 29.6 Gy for thymectomized rats. None of these differences are significant. It appears that neonatal thymectomy, in spite of its firm suppression of the cellular immunity, has no major influence on the development of radiation myelopathy in rats.