Functional Heterogeneity in CD4-bearing T Lymphocytes 
Second, when during development or activa- 
tion do subsets of CD4 -bearing T cells arise? A 
particularly interesting question is whether the 
commitment of CD4 -bearing T cells to the Thl 
and Th2 subsets is a consequence of antigen 
priming. Analysis of memory and virgin CD4- 
bearing T cells indicates that the functional spe- 
cialization characteristic of Thl and Th2 subsets 
resides mainly in the memory population. This 
suggests that contact with foreign antigen initi- 
ates a commitment of CD4-bearing T cells to a 
particular effector response. 
The form an immune response takes must be 
appropriate to the microorganism that is causing 
the disease. This is seen clearly in leprosy, where 
one response produces abundant antibody and, at 
the same time, overwhelming growth of the lep- 
rosy bacterium in macrophages. This is probably 
an example of selective activation of the helper 
(Th2), rather than the inflammatory (Thl), sub- 
set of CD4 T cells. What controls the form such a 
response will take? Model systems to explore 
these questions are needed, so that an inappropri- 
ate immune response can be redirected to be- 
come curative. Future research in this laboratory 
will focus on this question of the control of CD4 
T cell subset activation and regulation. 
Studies analyzing those factors important in the 
generation of memory and effector CDA^ T lym- 
phocytes and those analyzing the selective activa- 
tion of CD4 T cell subsets are supported by grants 
from the National Institutes of Health. 
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