T-lymphocyte alloresponses of Campath-1H-treated kidney transplant patients.
BACKGROUND
Kidney transplant patients given Campath-1H (Alemtuzumab) immunodepletion therapy and long-term rapamycin monotherapy have excellent graft survival and function at three years. As an initial step in understanding the characteristics of repopulated T lymphocytes in these patients, we performed several assays to assess alloreactivity.


METHODS
We measured T-cell responses using CFSE-labeled recipient lymphocytes in a direct one-way MLR, and also analyzed the kinetics of expression of IFN-gamma. We examined the T-cell responses of Campath-treated transplant patients on monotherapy versus those treated with anti-CD25 (Basiliximab) induction therapy and maintenance immunosuppression consisting of cyclosporine A, mycophenolate mofetil, and steroids.


RESULTS
On average, proliferative responses to donor antigen were equal between Campath and control groups. However, the Campath group displayed a greater response to third party compared to donor antigen (CD3 P = 0.04, CD4 P = 0.07, CD8 P < 0.01), whereas the control group did not display a greater response to third party (CD3 P = 0.69, CD4 P = 0.72, CD8 P = 0.60). Interestingly, more Campath patients (4 of 15) than control patients (0 of 8) displayed donor specific unresponsiveness as gauged by IFN-gamma expression and T-cell proliferation (P = 0.15).


CONCLUSIONS
These studies suggest that Campath-1H in conjunction with rapamycin monotherapy retains intact immune responses to third party alloantigen, yet may promote hyporesponsiveness to donor antigen.
Bloom
Debra D
DD
University of Wisconsin-Madison, Department of Surgery, Transplant Division, Madison, WI, USA. bloom@surgery.wisc.edu
Hu
Huaizhong
H
Fechner
John H
JH
Knechtle
Stuart J
SJ
D000293:Adolescent; D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D007700:Kinetics; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D016207:Cytokines; D007166:Immunosuppressive Agents; D007519:Isoantigens; D000074323:Alemtuzumab