Bloom, B.R., and Oldstone, M.B.A. 1991. Immunity 
to infection. Curr Opin Immunol 3:453-454. 
Bloom, B.R., Salgame, P., and Diamond, B. 1992. 
Revisiting and revising suppressor T cells. Im- 
munol Today 13:131-136. 
Chan, J., Xing, Y., Magliozzo, R.S., and Bloom, B.R. 
1992. Killing of virulent Mycobacterium tuber- 
culosis by reactive nitrogen intermediates pro- 
duced by activated murine macrophages. / Exp 
Med 175:1111-1122. 
Cirillo, J.D., Barletta, R.G., Bloom, B.R., and Ja- 
cobs, W.R., Jr. 1 99 1 . A novel transposon trap for 
mycobacteria: isolation and characterization of 
IS1096.J Bacteriol 173:7772-7780. 
Convit, J., Sampson, C, Zuniga, M., Smith, P.G., 
Plata, J., Silva, J., Molina, J., Pinardi, M.E., Bloom, 
B.R., and Salgado, A. 1992. Immunoprophylactic 
trial with combined Mycobacterium leprae/^CG 
vaccine against leprosy: preliminary results. Lan- 
cet 339:446-450. 
Jacobs, W.R., Jr., Kalpana, G.V., Cirillo, J. D., Pas- 
copella, L., Snapper, S.B., Udani, R.A., Jones, W., 
Barletta, R.G., and Bloom, B.R. 1991. Genetic 
systems for mycobacteria. Methods Enzymol 
204:537-555. 
Mehra, V., Bloom, B.R., Bajardi, A.C., Grisso, C.L., 
Sieling, P.A., Alland, D., Convit, J., Fan, X.-D., 
Hunter, S.W., Brennan, PJ., Rea, T.H., and Mod- 
lin, R.L. 1992. A major T cell antigen oi Mycobac- 
terium leprae is a 10-kD heat-shock cognate ^m- 
tein. J Exp Med 175:275-284. 
Salgame, P., Abrams, J.S., Clayberger, C, Goldstein, 
H., Convit, J., Modlin, R.L., and Bloom, B.R. 
1991- Differing lymphokine profiles of func- 
tional subsets of human CD4 and CD8 T cell 
clones. Science 254:279-282. 
Sullivan, L., Sano, S., Pirmez, C, Salgame, P., 
Mueller, C, Hofman, F., Uyemura, K., Rea, T.H., 
Bloom, B.R., and Modlin, R.L. 1991. Expression 
of adhesion molecules in leprosy lesions. Infect 
Immun 59:4154-4160. 
Yamamura, M., Uyemura, K., Deans, R.J., Weinberg, 
K., Rea, T.H., Bloom, B.R., and Modlin, R.L. 
1991- Defining protective responses to patho- 
gens: cytokine profiles in leprosy lesions. Science 
254:277-279. 
DEVELOPMENT OF LYMPHOCYTE SUBSETS 
H. Kim BoTTOMLY, Ph.D., Associate Investigator 
Studies in Dr. Bottomly's laboratory focus on the 
development and analysis of T lymphocyte subsets. 
These studies include differentiation of mature a/3 T 
cells in the periphery into memory or effector 
T cells, as well as differentiation of subsets during 
intrathymic development; studies with human as 
well as murine T cells are included. Since these dif- 
ferent T cell subsets perform distinct functions in 
host defense, characterizing their development and 
selective activation is crucial to understanding their 
behavior in infection and immunity. 
Peripheral Control of CD4 T Cell 
Subset Activation 
Studies in Dr. Bottomly's laboratory defined two 
populations of cloned CD4 T cells performing dis- 
tinct functions and producing distinct cytokines 
now called Thl and Th2. Thl cells are specialized 
for macrophage activation, while Th2 cells are more 
effective at activating B cells to secrete antibody. 
Subsequent studies in Dr. Bottomly's laboratory 
have focused on whether such populations exist 
among normal antigen-specific CD4 T cells in vivo 
and what determines which subset will become ac- 
tivated during an immune response. 
Using the immune response to a specific antigen, 
human collagen type IV, Dr. Bottomly has shown 
that a single peptide fragment of this protein acti- 
vates Thl -like cells in some strains of mice and Th2- 
like cells in other strains. The genes determining 
which type of CD4 T cell becomes activated encode 
the major histocompatibility complex (MHC) class 
II glycoprotein 1-A, which binds the peptide and 
presents it to CD4 T cell receptors. Thus, in this 
system at least, the determination of effector cell 
subtype must involve the actual ligand presented 
to the T cell receptor. The main focus of this 
line of research is to determine how a given MHC 
class II molecule could affect the outcome of 
immunization. 
Three possible explanations have been consid- 
ered. First, the specificity of the T cell receptor is 
somehow linked to the effector functions of the cell 
that bears it. This explanation is unlikely, since 
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