Co-stimulation with anti-CD28 (Kolt-2) enhances DNA synthesis by defective T cells in common variable immunodeficiency.
In normal T cells, an anti-CD28 MoAb (Kolt-2) will synergize with the mitogenic stimuli phytohaemagglutinin (PHA), anti-CD3 (OKT3) or a combination of anti-CD2 antibodies (OKT11 and GT2) in the induction of DNA synthesis. A subgroup of patients with common variable immunodeficiency (CVID) show a defect in DNA synthesis by T cells stimulated in vitro with the above mitogens. We have now investigated whether anti-CD28 will correct the defect. This strategy partially restored DNA synthesis, providing evidence that the CD28 co-stimulatory pathway in CVID T cells is normal. Ligation of CD28 acts through co-stimulating IL-2 secretion. The natural ligand (B7) for CD28 on antigen-presenting cells from CVID patients is expressed normally. We conclude that the defect in CVID T cells lies in pathways that lead to transcription of the IL-2 gene other than that induced by ligation of CD28 with Kolt-2.
North
M E
ME
Immune Deficiency Diseases Research Group, Clinical Research Centre, Harrow, Middlesex, UK.
Akbar
A N
AN
Borthwick
N
N
Sagawa
K
K
Funauchi
M
M
Webster
A D
AD
Farrant
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D018801:CD2 Antigens; D018106:CD28 Antigens / Q000032:analysis / Q000502:physiology*; D017074:Common Variable Immunodeficiency / Q000276:immunology*; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D011971:Receptors, Immunologic / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018106:CD28 Antigens; D007376:Interleukin-2; D011971:Receptors, Immunologic; D004247:DNA