Anti-CD4 Anticorps [OX-35] (A86697)

The aim of this study was to analyze the differential effects of three anti-CD4 monoclonal antibodies (mAbs) (with distinct epitope specifities) in the treatment of rat adjuvant arthritis (AA) and on T-cell function and signal transduction. Rat AA was preventively treated by intraperitoneal injection of the anti-CD4 mAbs W3/25, OX35, and RIB5/2 (on days -1, 0, 3, and 6, i.e. 1 day before AA induction, on the day of induction [day 0], and thereafter). The effects on T-cell reactivity in vivo (delayed-type hypersensitivity), ex vivo (ConA-induced proliferation), and in vitro (mixed lymphocyte culture) were assessed. The in vitro effects of anti-CD4 preincubation on T-cell receptor (TCR)/CD3-induced cytokine production and signal transduction were also analyzed. While preventive treatment with OX35 and W3/25 significantly ameliorated AA from the onset, treatment with RIB5/2 even accelerated the onset of AA by approximately 2 days (day 10), and ameliorated the arthritis only in the late phase (day 27). Differential clinical effects at the onset of AA were paralleled by a differential influence of the mAbs on T-cell functions, i.e. in comparison with OX35 and W3/25, the 'accelerating' mAb RIB5/2 failed to increase the delayed-type hypersentivity (DTH) to Mycobacterium tuberculosis, increased the in vitro tumor necrosis factor (TNF)-alpha secretion, and more strongly induced NF-kappaB binding activity after anti-CD4 preincubation and subsequent TCR/CD3-stimulation. Depending on their epitope specificity, different anti-CD4 mAbs differentially influence individual proinflammatory functions of T cells. This fine regulation may explain the differential efficacy in the treatment of AA and may contribute to the understanding of such treatments in other immunopathologies.

The objective of the present study was to assess the biocompatibility and regenerative potential of decellularized bovine pericardial scaffold in comparison with glutaraldehyde-treated and fresh bovine pericardial implants using short-term intramuscular implantation testing in a rat model. The inflammatory and immune responses were assessed using histopathological examination, special stains for connective tissue, histomorphometric evaluation, and immunohistochemistry. The decellularized pericardium showed an active tissue remodeling response with complete cellular invasion, minimum connective tissue encapsulation, extensive fibrovascular tissue formation, and collagen deposition. On the contrary, the glutaraldehyde-treated pericardial implants showed incomplete degradation and cellular invasion, while the fresh pericardial implants elicited a severe foreign body reaction. The results of immunohistochemical staining revealed a minimum T helper (CD4+) lymphocyte response in decellularized pericardial implants compared with its glutaraldehyde-treated and fresh counterparts. The decellularized bovine pericardium was better accepted as a prosthetic scaffold, which permitted maximum collagen deposition and active tissue remodeling by invading host cells and showed good tissue integration in vivo compared with glutaraldehyde-treated and fresh/untreated pericardium.

Immunotoxicology has developed into an integral regulatory requirement of the toxicological assessment of xenobiotics. Histopathological assessment of lymphoid tissues can provide genuine insight into perturbations of lymphoid cell populations. To facilitate retrospective examination of lymphoid organs should concerns over immunotoxicity be raised, we have endeavored to develop a panel of immunohistochemical techniques to demonstrate T-cells and T-cell subsets in formalin-fixed, paraffin-embedded rat lymphoid tissues. We were successful in developing methods for CD3 and CD8 but failed to arrive at a satisfactory technique for the direct demonstration of CD4 in these tissues. Taking the assumption that the majority of mature T-cells are either CD4+ or CD8+, we have combined our methods for CD3 and CD8 in a novel dual-labeling IHC method to simultaneously demonstrate CD3, CD8, and, by implication, CD4 in rat spleen, thymus, lymph node, and Peyer's patch.