Anti-TNFalpha therapy modulates the phenotype of peripheral blood CD4+ T cells in patients with posterior segment intraocular inflammation.
OBJECTIVE
Posterior segment intraocular inflammation (PSII) is a putative Th1 CD4+ cell mediated autoimmune disorder. In experimental autoimmune uveoretinitis, neutralization of tumor necrosis factor (TNF)-alpha induces suppression of Th1 cells, macrophage activation, and target organ damage. Previous studies implicated an efficacy of anti-TNFalpha therapies in patients with PSII. This study investigated the immunomodulatory effect of anti-TNFalpha therapy to find predictors of effective immunosuppression in PSII.


METHODS
Fifteen patients with PSII refractory to conventional immunosuppressive therapy received a single infusion of a recombinant protein generated by fusing the p55 TNFalpha receptor with human IgG1. During 17 treatment periods, visual acuity (logarithm of the minimum angle of resolution [logMAR]) was monitored as a response criterion. Phenotype markers of CD4+ T cells were analyzed before and 2, 4, and 12 weeks after therapy. Expression of intracellular cytokines (interferon [IFN]-gamma, interleukin [IL]-10, and TNFalpha) and Th1/Th2-specific chemokine receptors (CXCR3, CCR4, and CCR5) on peripheral blood CD4+ T cells was determined using flow cytometry.


RESULTS
The fraction of IL-10-expressing CD4+ T cells was increased during 12 of 17 treatment periods within 2 weeks after treatment. During eight treatment periods, this increase was associated with an improvement of visual acuity of at least 0.2 logMAR within 4 weeks (P = 0.029). The ratio between IL-10- and IFNgamma-expressing CD4+ T cells was significantly increased 2 weeks after therapy (P = 0.015). There was no significant change of CXCR3, CCR4, or CCR5 expression.


CONCLUSIONS
Neutralizing TNFalpha activity in PSII increases the fraction of peripheral blood CD4+ T cells expressing IL-10, which correlates with a recovery of visual function.
Greiner
Kathrin
K
Department of Ophthalmology, University of Aberdeen, Aberdeen, United Kingdom.
Murphy
Conor C
CC
Willermain
Francois
F
Duncan
Linda
L
Plskova
Jarka
J
Hale
Geoff
G
Isaacs
John D
JD
Forrester
John V
JV
Dick
Andrew D
AD
D000328:Adult; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000627:therapeutic use; D007142:Immunoglobulin gamma-Chains; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019707:Receptors, Chemokine / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D012173:Retinitis / Q000276:immunology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014605:Uveitis / Q000276:immunology / Q000628:therapy*
D016207:Cytokines; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D019707:Receptors, Chemokine; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C099374:Ro 45-2081