The costimulatory signal CD28 is fully functional but cannot correct the impaired antigen response in T cells of patients with common variable immunodeficiency.
A wide spectrum of different immunologic abnormalities have been postulated as being responsible for the impairment of specific antibody production and the decrease in all or selected immunoglobulin isotypes present in common variable immunodeficiency (CVID). These abnormalities include impaired B cell differentiation and/or function, defective macrophage function, and significant T cell defects. The aim of the present study was to delineate whether the accessory molecule CD28 is involved in the impaired antigen response of T cells from patients with CVID. Our results demonstrate that CD28 costimulation was functional in T cells stimulated with anti-CD3 or anti-TCR MoAb, but could not correct the impaired response of patients' peripheral blood T cells to tetanus toxoid. Analysis of patients' long-term cultured T cells further confirmed these results. Exogenous rIL-2, another costimulus, augmented but did not correct the defective proliferation and lymphokine production in patients' antigen-driven peripheral blood T lymphocytes or in long-term cultured T cells. These findings indicate that the CD28 signalling pathway in these patients' T cells is unimpaired, and that costimulation via CD28 cannot correct the defect occurring in the course of TCR-mediated T cell activation.
Fischer
M B
MB
Institute of Immunology, University of Vienna, Austria.
Wolf
H M
HM
Eggenbauer
H
H
Thon
V
V
Vogel
E
E
Lokaj
J
J
Litzman
J
J
Mannhalter
J W
JW
Eibl
M M
MM
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D018106:CD28 Antigens / Q000502:physiology*; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D007376:Interleukin-2