Cytokine Regulation of Effector Functions in Immune Responses 
methods are feasible for detecting single cyto- 
kines produced by one cell, and we are currently 
adapting them to simultaneous measurement of 
multiple cytokines. Since there is considerable 
evidence of several different cytokine secretion 
phenotypes, 5-10 cytokines must be analyzed 
from each cell to obtain a true picture of T cell 
diversity. Once developed, this methodology 
will be applied to the differentiation of T cells 
during normal immune responses, allowing the 
signals that influence differentiation to be 
determined. 
The characteristic cytokines of THl and TH2 
are major determinants of the function of these 
cells. For example, IL-4, IL-5, and IL-10, pro- 
duced by TH2 cells, contribute to the production 
of IgE, mast cells, and eosinophils — all asso- 
ciated with the development of allergy. IFN-7 is a 
major contributor to DTH reactions, inhibits 
many of the functions of IL-4, and inhibits TH2 
cells directly. We have been interested for some 
time in additional cytokines of the two T cell 
types. 
Recently we have been working on P6OO, origi- 
nally discovered as a clone in a cDNA library of 
activated TH2 cells. P600 is particularly interest- 
ing, since it is expressed only after activation and 
is not produced by THl cells. The sequence of 
the open reading frame in the P600 cDNA clone 
encodes a small protein with a leader sequence 
characteristic of secreted or membrane proteins. 
Since all of these properties suggest that P600 
may be an additional TH2-specific cytokine, we 
decided to test for possible functions of the P6OO 
protein. 
We transfected the P6OO cDNA clone into mon- 
key cells and observed secretion of a new protein 
of the expected size. After screening in a wide 
variety of biological assays, we found that P600 
induces the production of large numbers of ad- 
herent cells from bone marrow. The functions of 
these cells are currently under investigation to 
determine how the effects of P6OO fit into the 
overall pattern of TH2 functions during immune 
responses. 
The different T cell cytokine secretion pheno- 
types were originally discovered in the mouse, 
and initially there was some doubt that similar 
phenotypes exist in humans. However, recent 
data on human T cell clones and immune re- 
sponses have made it clear that the THl and TH2 
patterns are also important in himian diseases. Ap- 
parently several parasitic diseases strongly in- 
duce TH 1 - or TH 2 -biased responses, and only one 
of these responses is usually able to clear the in- 
fectious agent. Recent data indicate that these 
two cytokine patterns are also important in lep- 
rosy. Thus a knowledge of the regulation of these 
patterns will have considerable potential for the 
design of better immunomodulatory treatments 
and vaccines. 
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