Expression of CD134 (0X-40) on T cells during the first 100 days following allogeneic bone marrow transplantation as a marker for lymphocyte activation and therapy-resistant graft-versus-host disease.
CD134 (OX-40) is an activation-associated antigen which functions as a costimulatory receptor for CD4+ T cells. In order to determine the expression of CD134 during immune recovery following allogeneic bone marrow transplantation (BMT), we measured its expression on T cells and T cell subsets during the first 100 days following BMT in 26 patients. CD4+CD134+ T could be seen approximately 14 days following BMT cells in patients who did not develop GvHD which required therapy (n = 20). The percentage of CD4+CD134+ cells continued to increase up to the fourth week following BMT to a maximum of 40-50% of CD4+ T cells (normal = 1-8%). Two patients who developed Grade I-II GvHD and who responded to treatment with pulsed high-dose methylprednisolone (MPD) showed a decline of approximately 40% in CD4+CD134+ T cells was seen within 48 hours of treatment. Four patients who developed GvHD that was not responsive to MPD and who later developed high IV GvHD showed increasing CD4+CD134+ T cells up to 85% of the CD4+ T cells. Additionally, rapid increases in CD134+ T cells following antibody-based T cell therapy were associated with GvHD recurrence. In no cases was the percentage of CD134+ CD4+ T cells predictive of clinical GvHD. In this exploratory study, we have shown that CD134, although not predictive of the initial onset of GvHD, may be a useful tool for monitoring the response to early GvHD therapy and identification of patients at risk for reemergence of GvHD who may benefit from anti-T cell therapy. Cytometry (Comm. Clin. Cytometry) 38: 238-243, 1999.
Lamb
L S
LS
Division of Transplantation Medicine, Palmetto Richland Memorial Hospital, Center for Cancer Treatment and Research, University of South Carolina School of Medicine, Columbia, South Carolina. lslamb@compuserve.com
Abhyankar
S A
SA
Hazlett
L
L
O'Neal
W
W
Folk
R S
RS
Vogt
S
S
Parrish
R S
RS
Bridges
K
K
Henslee-Downey
P J
PJ
Gee
A P
AP
D015415:Biomarkers / Q000032:analysis; D016026:Bone Marrow Transplantation; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002469:Cell Separation; D002908:Chronic Disease; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion / Q000379:methods; D008775:Methylprednisolone / Q000627:therapeutic use; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D019172:Transplantation Conditioning; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis*
D015415:Biomarkers; D007166:Immunosuppressive Agents; D011971:Receptors, Immunologic; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D008775:Methylprednisolone