Blood, 15 March 2001, Vol. 97, No. 6, pp. 1523-1523
IL-7: success without a formal education
Decimation of the T-cell pool following intensive chemotherapy,
bone marrow transplantation, or infection with HIV renders the patient
highly susceptible to a variety of life-threatening infectious
pathogens and/or fatal malignancies. Restoration of normal T-cell
immunity can occur by 2 distinct paths: The first is an educational
process whereby now-naïve T-cell precursors in the bone marrow
traffic through the thymus to acquire the diverse receptor repertoire
necessary to face the multitude of pathogens. The second pathway relies
on the few surviving T-cell soldiers in the blood, wounded and fragile
but with the potential to regroup and expand into a competent
lymphocyte pool in the absence of a thymus. How these few peripheral T
cells can avoid remedial education in the thymus, survive, and grow to
contribute to host immune restoration has remained a mystery. Fry and
colleagues (page 1525) examine restoration of T-cell immunity in the
absence of thymic education. They demonstrate that, in thymectomized
mice receiving exogenous IL-7, low numbers of peripheral T cells can attack target antigens via at least 3 mechanisms: better T-cell expansion, enhanced T-cell survival, and improvement in target antigen-presenting cells. The absence of exogenous IL-7 renders the
thymectomized host unable to recognize the target antigen.
This has potentially exciting clinical application in adults with
T-cell deficiencies and a restricted amount of thymic function. Should
the study results in the mouse model of HY-disparate skin grafts prove
comparable in models of high-dose chemotherapy, one could soon envision
clinical trials of high-dose chemotherapy followed by low-dose IL-7
therapy to assess the cytokine's effect on quantitative and
qualitative aspects of peripheral-T-cell reconstitution. More effective
T-cell recovery in states of minimal residual malignant disease that
often follow high-dose chemotherapy might impact on disease-free and
overall survival. Comparable studies in the setting of allogeneic
transplantation would need to balance the possible advantages of
improved T-cell function in combating life-threatening infections
and in mediating graft-versus-tumor effects with the potential adverse
consequences of intensifying graft-versus-host disease or graft
rejection. But in patients with HIV infection on effective
antiretroviral therapy, low-dose IL-7 therapy might contribute to a
more sustained and diverse T-cell recovery by enhancing both the
proliferative response and the threshold for apoptosis.
Michael A. Caligiuri
Ohio State University
