Evidence for increased expression of regulatory cytokine receptors interleukin-12R and interleukin-18R in common variable immunodeficiency.
We investigated the expression of T helper (Th)1/Th2 regulatory cytokine receptors on lymphocytes from patients with common variable immunodeficiency (CVID), a disorder associated with raised Th1 cytokine production, comparing the results with those from healthy individuals and atopic asthmatics, the latter generally considered to have a Th2-driven disease. We proposed that alterations in some of the relevant receptors might be related to the observed imbalances in Th1/Th2 cytokines. Cells from CVID patients showed an increase in the percentages of CD212 [interleukin (IL)-12Rbeta1] cells within the CD4+ CD45RA+ and CD8+ CD45RA+ subsets (24% and 41%, respectively), as compared to CD4+ CD45RA+ and CD8+ CD45RA+ in healthy subjects (6% and 23%, respectivey). Approximately 21% of the CD4+ CD45RA+ naïve cells expressed IL-18Ralpha, compared with 11% in healthy subjects. In contrast, the cytokine-receptor expression in asthmatics was similar to that of controls. In spite of the above differences, after 72 h of stimulation with anti-CD3 and anti-CD28, cytokine receptor up-regulation was similar in all three groups, with up to 80% of both CD45RA+ and CD45RO+ lymphocytes expressing CD212 (IL-12Rbeta1) and IL-18Ralpha. Approximately 50% of the 'naïve', and 25% of the 'memory' subpopulations up-regulated IL-12Rbeta2. These findings provide further evidence of a polarization towards a Th1 immune response in CVID, the mechanism possibly involving up-regulation of IL-12-mediated pathways.
McQuaid
A
A
Department of Immunology, Royal Free Hospital, Pond Street, London, UK.
Tormey
V J
VJ
Trafford
B
B
Webster
A D
AD
Bofill
M
M
D000328:Adult; D000368:Aged; D001249:Asthma / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D005260:Female; D006801:Humans; D053727:Interleukin-18 Receptor alpha Subunit; D017493:Leukocyte Common Antigens / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000097:blood*; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D018417:Th1 Cells / Q000276:immunology; D015854:Up-Regulation
C508572:IL18R1 protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D017493:Leukocyte Common Antigens